Fioranelli M, Roccia MG, Flavin D, Cota L. Regulation of Inflammatory Reaction in Health and Disease. Int J Mol Sci. 2021;22:5277.
Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018;14:576–90.
Fischer A, Wannemacher J, Christ S, Koopmans T, Kadri S, Zhao J, et al. Neutrophils direct preexisting matrix to initiate repair in damaged tissues. Nat Immunol. 2022;23:518–31.
Zhu Z, Zhou S, Li S, Gong S, Zhang Q. Neutrophil extracellular traps in wound healing. Trends Pharmacol Sci. 2024;45:1033–45.
Herrero-Cervera A, Soehnlein O, Kenne E. Neutrophils in chronic inflammatory diseases. Cell Mol Immunol. 2022;19:177–91.
Ng M, Cerezo-Wallis D, Ng LG, Hidalgo A. Adaptations of neutrophils in cancer. Immunity. 2025;58:40–58.
Zhou Y, Shen G, Zhou X, Li J. Therapeutic potential of tumor-associated neutrophils: dual role and phenotypic plasticity. Sig Transduct Target Ther. 2025;10:178.
Jaillon S, Ponzetta A, Di Mitri D, Santoni A, Bonecchi R, Mantovani A. Neutrophil diversity and plasticity in tumor progression and therapy. Nat Rev Cancer. 2020;20:485–503.
Overbeeke C, Tak T, Koenderman L. The journey of neutropoiesis: how complex landscapes in bone marrow guide continuous neutrophil lineage determination. Blood. 2022;139:2285–93.
Calzetti F, Finotti G, Cassatella MA. Current knowledge on the early stages of human neutropoiesis. Immunol Rev. 2023;314:111–24.
Signoretto I, Calzetti F, Finotti G, Lonardi S, Balanzin C, Bianchetto-Aguilera F, et al. Uncovering two neutrophil-committed progenitors that immediately precede promyelocytes during human neutropoiesis. Cell Mol Immunol. 2025;22:316–29.
Mehta HM, Corey SJ. G-CSF, the guardian of granulopoiesis. Semin Immunol. 2021;54:101515.
Lieschke GJ, Grail D, Hodgson G, Metcalf D, Stanley E, Cheers C, et al. Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization. Blood. 1994;84:1737–46.
Liu F, Wu HY, Wesselschmidt R, Kornaga T, Link DC. Impaired production and increased apoptosis of neutrophils in granulocyte colony-stimulating factor receptor-deficient mice. Immunity. 1996;5:491–501.
Yong KL, Linch DC. Differential effects of granulocyte- and granulocyte‒macrophage colony‒stimulating factors (G-CSF and GM-CSF) on neutrophil adhesion in vitro and in vivo. Eur J Hematol. 1992;49:251–9.
Yuo A, Kitagawa S, Ohsaka A, Ohta M, Miyazono K, Okabe T, et al. Recombinant human granulocyte colony-stimulating factor as an activator of human granulocytes: potentiation of responses triggered by receptor-mediated agonists and stimulation of C3bi receptor expression and adherence. Blood. 1989;74:2144–9.
Evrard M, Kwok IWH, Chong SZ, Teng KWW, Becht E, Chen J, et al. Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions. Immunity. 2018;48:364–79.e8.
Yamanaka R, Barlow C, Lekstrom-Himes J, Castilla LH, Liu PP, Eckhaus M, et al. Impaired granulopoiesis, myelodysplasia, and early lethality in CCAAT/enhancer binding protein epsilon-deficient mice. Proc Natl Acad Sci USA. 1997;94:13187–92.
Hirai H, Zhang P, Dayaram T, Hetherington CJ, Mizuno S, Imanishi J, et al. C/EBPbeta is required for ‘emergency’ granulopoiesis. Nat Immunol. 2006;7:732–9.
Morosetti R, Park DJ, Chumakov AM, Grillier I, Shiohara M, Gombart AF, et al. A novel, myeloid transcription factor, C/EBP epsilon, is upregulated during granulocytic, but not monocytic, differentiation. Blood. 1997;90:2591–600.
Borregaard N, Kjeldsen L, Rygaard K, Bastholm L, Nielsen MH, Sengeløv H, et al. Stimulus-dependent secretion of plasma proteins from human neutrophils. J Clin Invest. 1992;90:86–96.
Borregaard N, Sørensen OE, Theilgaard-Mönch K. Neutrophil granules: a library of innate immunity proteins. Trends Immunol. 2007;28:340–5.
Rørvig S, Østergaard O, Heegaard NHH, Borregaard N. Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane: correlation with transcriptome profiling of neutrophil precursors. J Leukoc Biol. 2013;94:711–21.
Sengeløv H, Kjeldsen L, Borregaard N. Control of exocytosis in early neutrophil activation. J Immunol. 1993;150:1535–43.
Söllner T, Whiteheart SW, Brunner M, Erdjument-Bromage H, Geromanos S, Tempst P, et al. SNAP receptors implicated in vesicle targeting and fusion. Nature. 1993;362:318–24.
Gerst JE. SNAREs and SNARE regulators in membrane fusion and exocytosis. Cell Mol Life Sci. 1999;55:707–34.
Scapini P, Bazzoni F, Cassatella MA. Regulation of B-cell-activating factor (BAFF)/B lymphocyte stimulator (BLyS) expression in human neutrophils. Immunol Lett. 2008;116:1–6.
Cassatella MA. On the production of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 L) by human neutrophils. J Leukoc Biol. 2006;79:1140–9.
Tamassia N, Cassatella MA, Bazzoni F. Fast and accurate quantitative analysis of cytokine gene expression in human neutrophils. Methods Mol Biol. 2014;1124:451–67.
Tecchio C, Micheletti A, Cassatella MA. Neutrophil-Derived Cytokines: Facts Beyond Expression. Front Immunol. 2014;5:508.
Hacbarth E, Kajdacsy-Balla A. Low density neutrophils in patients with systemic lupus erythematosus, rheumatoid arthritis, and acute rheumatic fever. Arthritis Rheum. 1986;29:1334–42.
Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: ‘N1’ versus ‘N2’ TAN. Cancer Cell. 2009;16:183–94.
Jablonska J, Leschner S, Westphal K, Lienenklaus S, Weiss S. Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model. J Clin Invest. 2010;120:1151–64.
Antuamwine BB, Bosnjakovic R, Hofmann-Vega F, Wang X, Theodosiou T, Iliopoulos I, et al. N1 versus N2 and PMN-MDSC: A critical appraisal of current concepts on tumor-associated neutrophils and new directions for human oncology. Immunol Rev. 2023;314:250–79.
Wigerblad G, Cao Q, Brooks S, Naz F, Gadkari M, Jiang K, et al. Single-Cell Analysis Reveals the Range of Transcriptional States of Circulating Human Neutrophils. J Immunol. 2022;209:772–82.
Metzemaekers M, Cambier S, Blanter M, Vandooren J, de Carvalho AC, Malengier-Devlies B, et al. Kinetics of peripheral blood neutrophils in severe coronavirus disease 2019. Clin Transl Immunol. 2021;10:e1271.
El-Benna J, Hurtado-Nedelec M, Marzaioli V, Marie J-C, Gougerot-Pocidalo M-A, Dang PM-C. Priming of the neutrophil respiratory burst: role in host defense and inflammation. Immunol Rev. 2016;273:180–93.
Quiñonez-Flores CM, González-Chávez SA, Del Río Nájera D, Pacheco-Tena C. Oxidative Stress Relevance in the Pathogenesis of the Rheumatoid Arthritis: A Systematic Review. Biomed Res Int. 2016;2016:6097417.
Zeida A, Trujillo M, Ferrer-Sueta G, Denicola A, Estrin DA, Radi R. Catalysis of Peroxide Reduction by Fast Reacting Protein Thiols. Chem Rev. 2019;119:10829–55.
Winterbourn CC, Kettle AJ, Hampton MB. Reactive Oxygen Species and Neutrophil Function. Annu Rev Biochem. 2016;85:765–92.
Metzemaekers M, Malengier-Devlies B, Gouwy M, De Somer L, de Queiroz, Cunha F, et al. Fast and furious: The neutrophil and its armamentarium in health and disease. Med Res Rev. 2023;43:1537–606.
Poli V, Zanoni I. Neutrophil intrinsic and extrinsic regulation of NETosis in health and disease. Trends Microbiol. 2023;31:280–93.
Wang H, Kim SJ, Lei Y, Wang S, Wang H, Huang H, et al. Neutrophil extracellular traps in homeostasis and disease. Sig Transduct Target Ther. 2024;9:235.
Fresneda Alarcon M, McLaren Z, Wright HL. Neutrophils in the Pathogenesis of Rheumatoid Arthritis and Systemic Lupus Erythematosus: Same Foe Different M.O. Front Immunol. 2021;12:649693.
Zhao J, Jiang P, Guo S, Schrodi SJ, He D. Apoptosis, Autophagy, NETosis, Necroptosis, and Pyroptosis Mediated Programmed Cell Death as Targets for Innovative Therapy in Rheumatoid Arthritis. Front Immunol. 2021;12:809806.
Tu H, Ren H, Jiang J, Shao C, Shi Y, Li P. Dying to Defend: Neutrophil Death Pathways and their Implications in Immunity. Adv Sci. 2024;11:e2306457.
Dejas L, Santoni K, Meunier E, Lamkanfi M. Regulated cell death in neutrophils: From apoptosis to NETosis and pyroptosis. Semin Immunol. 2023;70:101849.
Zhang J, He J, Xia J, Chen Z, Chen X. Delayed apoptosis by neutrophils from COPD patients is associated with altered Bak, Bcl-xl, and Mcl-1 mRNA expression. Diagn Pathol. 2012;7:65.
Wright HL, Lyon M, Chapman EA, Moots RJ, Edwards SW. Rheumatoid Arthritis Synovial Fluid Neutrophils Drive Inflammation Through Production of Chemokines, Reactive Oxygen Species, and Neutrophil Extracellular Traps. Front Immunol. 2020;11:584116.
Mustafa M, Ahmad R, Tantry IQ, Ahmad W, Siddiqui S, Alam M, et al. Apoptosis: A Comprehensive Overview of Signaling Pathways, Morphological Changes, and Physiological Significance and Therapeutic Implications. Cells. 2024;13:1838.
Moon B, Yang S, Moon H, Lee J, Park D. After cell death: the molecular machinery of efferocytosis. Exp Mol Med. 2023;55:1644–51.
Muñoz LE, Lauber K, Schiller M, Manfredi AA, Herrmann M. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat Rev Rheumatol. 2010;6:280–9.
Barnes PJ, Burney PGJ, Silverman EK, Celli BR, Vestbo J, Wedzicha JA, et al. Chronic obstructive pulmonary disease. Nat Rev Dis Prim. 2015;1:15076.
Li Y, Wu Y, Huang J, Cao X, An Q, Peng Y, et al. A variety of death modes of neutrophils and their role in the etiology of autoimmune diseases. Immunol Rev. 2024;321:280–99.
Schuermans S, Kestens C, Marques PE. Systemic mechanisms of necrotic cell debris clearance. Cell Death Dis. 2024;15:557.
Liu J, Jiang Y, Diao Z, Chen D, Xia R, Wang B, et al. Gasdermin D-mediated neutrophil pyroptosis drives inflammation in psoriasis. eLife. 2024;13:RP101248.
Dworski R, Simon H-U, Hoskins A, Yousefi S. Eosinophil and neutrophil extracellular DNA traps in human allergic asthmatic airways. J Allergy Clin Immunol. 2011;127:1260–6.
Metzemaekers M, Gouwy M, Proost P. Neutrophil chemoattractant receptors in health and disease: double-edged swords. Cell Mol Immunol. 2020;17:433–50.
Filippi M-D. Neutrophil transendothelial migration: updates and new perspectives. Blood. 2019;133:2149–58.
Girbl T, Lenn T, Perez L, Rolas L, Barkaway A, Thiriot A, et al. Distinct Compartmentalization of the Chemokines CXCL1 and CXCL2 and the Atypical Receptor ACKR1 Determine Discrete Stages of Neutrophil Diapedesis. Immunity. 2018;49:1062–76.e6.
Sreeramkumar V, Adrover JM, Ballesteros I, Cuartero MI, Rossaint J, Bilbao I, et al. Neutrophils scan for activated platelets to initiate inflammation. Science. 2014;346:1234–8.
Joulia R, Guerrero-Fonseca IM, Girbl T, Coates JA, Stein M, Vázquez-Martínez L, et al. Neutrophil breaching of the blood vessel pericyte layer during diapedesis requires mast cell-derived IL-17A. Nat Commun. 2022;13:7029.
Proebstl D, Voisin M-B, Woodfin A, Whiteford J, D’Acquisto F, Jones GE, et al. Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo. J Exp Med. 2012;209:1219–34.
Graham GJ, Handel TM, Proudfoot AEI. Leukocyte Adhesion: Reconceptualizing Chemokine Presentation by Glycosaminoglycans. Trends Immunol. 2019;40:472–81.
Massena S, Christoffersson G, Hjertström E, Zcharia E, Vlodavsky I, Ausmees N, et al. A chemotactic gradient sequestered on endothelial heparan sulfate induces directional intraluminal crawling of neutrophils. Blood. 2010;116:1924–31.
Moseley R, Waddington RJ, Embery G. Degradation of glycosaminoglycans by reactive oxygen species derived from stimulated polymorphonuclear leukocytes. Biochim Biophys Acta. 1997;1362:221–31.
Yu WH, Woessner JF. Heparan sulfate proteoglycans as extracellular docking molecules for matrilysin (matrix metalloproteinase 7). J Biol Chem. 2000;275:4183–91.
Ramnath R, Foster RR, Qiu Y, Cope G, Butler MJ, Salmon AH, et al. Matrix metalloproteinase 9-mediated shedding of syndecan 4 in response to tumor necrosis factor α: a contributor to endothelial cell glycocalyx dysfunction. FASEB J. 2014;28:4686–99.
Henry CB, Duling BR. TNF-alpha increases the entry of macromolecules into the glycocalyx of luminal endothelial cells. Am J Physiol Heart Circ Physiol. 2000;279:H2815–23.
Manchanda K, Kolarova H, Kerkenpaß C, Mollenhauer M, Vitecek J, Rudolph V, et al. MPO (Myeloperoxidase) Reduces Endothelial Glycocalyx Thickness Dependent on Its Cationic Charge. Arterioscler Thromb Vasc Biol. 2018;38:1859–67.
Constantinescu AA, Vink H, Spaan JAE. Endothelial cell glycocalyx modulates immobilization of leukocytes at the endothelial surface. Arterioscler Thromb Vasc Biol. 2003;23:1541–7.
Vink H, Constantinescu AA, Spaan JA. Oxidized lipoproteins degrade the endothelial surface layer: implications for platelet-endothelial cell adhesion. Circulation. 2000;101:1500–2.
Wadowski PP, Kautzky-Willer A, Gremmel T, Koppensteiner R, Wolf P, Ertl S, et al. Sublingual microvasculature in diabetic patients. Microvasc Res. 2020;129:103971.
Lopez-Quintero SV, Cancel LM, Pierides A, Antonetti D, Spray DC, Tarbell JM. High glucose attenuates shear-induced changes in endothelial hydraulic conductivity by degrading the glycocalyx. PLoS One. 2013;8:e78954.
Shiohara M, Gombart AF, Sekiguchi Y, Hidaka E, Ito S, Yamazaki T, et al. Phenotypic and functional alterations of peripheral blood monocytes in neutrophil-specific granule deficiency. J Leukoc Biol. 2004;75:190–7.
Gallin JI, Fletcher MP, Seligmann BE, Hoffstein S, Cehrs K, Mounessa N. Human neutrophil-specific granule deficiency: a model to assess the role of neutrophil-specific granules in the evolution of the inflammatory response. Blood. 1982;59:1317–29.
Xue J, Schmidt SV, Sander J, Draffehn A, Krebs W, Quester I, et al. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity. 2014;40:274–88.
Warnatsch A, Ioannou M, Wang Q, Papayannopoulos V. Inflammation. Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis. Science. 2015;349:316–20.
Soehnlein O, Kai-Larsen Y, Frithiof R, Sorensen OE, Kenne E, Scharffetter-Kochanek K, et al. Neutrophil primary granule proteins HBP and HNP1-3 boost bacterial phagocytosis by human and murine macrophages. J Clin Invest. 2008;118:3491–502.
Headland SE, Jones HR, Norling LV, Kim A, Souza PR, Corsiero E, et al. Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis. Sci Transl Med. 2015;7:315ra190.
Marwick JA, Mills R, Kay O, Michail K, Stephen J, Rossi AG, et al. Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation. Cell Death Dis. 2018;9:665.
Rhys HI, Dell’Accio F, Pitzalis C, Moore A, Norling LV, Perretti M. Neutrophil Microvesicles from Healthy Control and Rheumatoid Arthritis Patients Prevent the Inflammatory Activation of Macrophages. EBioMedicine. 2018;29:60–9.
Yang W, Tao Y, Wu Y, Zhao X, Ye W, Zhao D, et al. Neutrophils promote the development of reparative macrophages mediated by ROS to orchestrate liver repair. Nat Commun. 2019;10:1076.
Joseph JE, Harrison P, Mackie IJ, Isenberg DA, Machin SJ. Increased circulating platelet-leucocyte complexes and platelet activation in patients with antiphospholipid syndrome, systemic lupus erythematosus and rheumatoid arthritis. Br J Hematol. 2001;115:451–9.
Herster F, Bittner Z, Codrea MC, Archer NK, Heister M, Löffler MW, et al. Platelets Aggregate With Neutrophils and Promote Skin Pathology in Psoriasis. Front Immunol. 2019;10:1867.
Stark K, Massberg S. Interplay between inflammation and thrombosis in cardiovascular pathology. Nat Rev Cardiol. 2021;18:666–82.
Etulain J, Martinod K, Wong SL, Cifuni SM, Schattner M, Wagner DD. P-selectin promotes neutrophil extracellular trap formation in mice. Blood. 2015;126:242–6.
Maugeri N, Franchini S, Campana L, Baldini M, Ramirez GA, Sabbadini MG, et al. Circulating platelets as a source of the damage-associated molecular pattern HMGB1 in patients with systemic sclerosis. Autoimmunity. 2012;45:584–7.
Yang B, Liu X, Mei Q. HMGB1-Positive Platelet Microparticles May Be a Biomarker of Inflammatory Bowel Disease. Inflamm Bowel Dis. 2020;26:e10.
Chen R, Kang R, Tang D. The mechanism of HMGB1 secretion and release. Exp Mol Med. 2022;54:91–102.
Stark K, Philippi V, Stockhausen S, Busse J, Antonelli A, Miller M, et al. Disulfide HMGB1 derived from platelets coordinates venous thrombosis in mice. Blood. 2016;128:2435–49.
Oh S-A, Seol S-I, Davaanyam D, Kim S, Lee W. J-K. Platelet-derived HMGB1 induces NETosis, exacerbating brain damage in the photothrombotic stroke model. Mol Med. 2025;31:46.
Tadie J-M, Bae H-B, Jiang S, Park DW, Bell CP, Yang H, et al. HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4. Am J Physiol Lung Cell Mol Physiol. 2013;304:L342–349.
Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, et al. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B-cell growth. J Exp Med. 1999;189:1747–56.
Cheema GS, Roschke V, Hilbert DM, Stohl W. Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum. 2001;44:1313–9.
Gross JA, Dillon SR, Mudri S, Johnston J, Littau A, Roque R, et al. TACI-Ig neutralizes molecules critical for B-cell development and autoimmune disease. Impaired B cell maturation in mice lacking BLyS. Immunity. 2001;15:289–302.
Thai L-H, Le Gallou S, Robbins A, Crickx E, Fadeev T, Zhou Z, et al. BAFF and CD4+ T cells are major survival factors for long-lived splenic plasma cells in a B-cell-depletion context. Blood. 2018;131:1545–55.
Gabay C, Krenn V, Bosshard C, Seemayer CA, Chizzolini C, Huard B. Synovial tissues concentrate secreted APRIL. Arthritis Res Ther. 2009;11:R144.
Gosselin EJ, Wardwell K, Rigby WF, Guyre PM. Induction of MHC class II on human polymorphonuclear neutrophils by granulocyte/macrophage colony-stimulating factor, IFN-gamma, and IL-3. J Immunol. 1993;151:1482–90.
Vono M, Lin A, Norrby-Teglund A, Koup RA, Liang F, Loré K. Neutrophils acquire the capacity for antigen presentation to memory CD4+ T cells in vitro and ex vivo. Blood. 2017;129:1991–2001.
Matsushima H, Geng S, Lu R, Okamoto T, Yao Y, Mayuzumi N, et al. Neutrophil differentiation into a unique hybrid population exhibiting dual phenotype and functionality of neutrophils and dendritic cells. Blood. 2013;121:1677–89.
Grieshaber-Bouyer R, Exner T, Hackert NS, Radtke FA, Jelinsky SA, Halyabar O, et al. Aging and interferon gamma response drive the phenotype of neutrophils in the inflamed joint. Ann Rheum Dis. 2022;81:805–14.
Opdenakker G, Van Damme J. Cytokine-regulated proteases in autoimmune diseases. Immunol Today. 1994;15:103–7.
Moffat A, Gwyer Findlay E. Evidence for antigen presentation by human neutrophils. Blood. 2024;143:2455–63.
Cai Y, Zhang J, Liang J, Xiao M, Zhang G, Jing Z, et al. The Burden of Rheumatoid Arthritis: Findings from the 2019 Global Burden of Diseases Study and Forecasts for 2030 by Bayesian Age-Period-Cohort Analysis. J Clin Med. 2023;12:1291.
Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, et al. Rheumatoid arthritis. Nat Rev Dis Prim. 2018;4:18001.
Terkeltaub R, Zachariae C, Santoro D, Martin J, Peveri P, Matsushima K. Monocyte-derived neutrophil chemotactic factor/interleukin-8 is a potential mediator of crystal-induced inflammation. Arthritis Rheum. 1991;34:894–903.
Koch AE, Kunkel SL, Burrows JC, Evanoff HL, Haines GK, Pope RM, et al. Synovial tissue macrophage as a source of the chemotactic cytokine IL-8. J Immunol. 1991;147:2187–95.
Metzemaekers M, Abouelasrar Salama S, Vandooren J, Mortier A, Janssens R, Vandendriessche S, et al. From ELISA to Immunosorbent Tandem Mass Spectrometry Proteoform Analysis: The Example of CXCL8/Interleukin-8. Front Immunol. 2021;12:644725.
Tchetverikov I, Ronday HK, Van El B, Kiers GH, Verzijl N, TeKoppele JM, et al. MMP profile in paired serum and synovial fluid samples of patients with rheumatoid arthritis. Ann Rheum Dis. 2004;63:881–3.
Metzemaekers M, Malengier-Devlies B, Yu K, Vandendriessche S, Yserbyt J, Matthys P, et al. Synovial Fluid Neutrophils From Patients With Juvenile Idiopathic Arthritis Display a Hyperactivated Phenotype. Arthritis Rheumatol. 2021;73:875–84.
Poubelle PE, Chakravarti A, Fernandes MJ, Doiron K, Marceau A-A. Differential expression of RANK, RANK-L, and osteoprotegerin by synovial fluid neutrophils from patients with rheumatoid arthritis and by healthy human blood neutrophils. Arthritis Res Ther. 2007;9:R25.
Chakravarti A, Raquil M-A, Tessier P, Poubelle PE. Surface RANKL of Toll-like receptor 4-stimulated human neutrophils activates osteoclastic bone resorption. Blood. 2009;114:1633–44.
Xu Z, Xu B, Lundström SL, Moreno-Giró À, Zhao D, Martin M, et al. A subset of type-II collagen-binding antibodies prevents experimental arthritis by inhibiting FCGR3 signaling in neutrophils. Nat Commun. 2023;14:5949.
Pérez-Sánchez C, Ruiz-Limón P, Aguirre MA, Jiménez-Gómez Y, Arias-de la Rosa I, Ábalos-Aguilera MC, et al. Diagnostic potential of NETosis-derived products for disease activity, atherosclerosis and therapeutic effectiveness in Rheumatoid Arthritis patients. J Autoimmun. 2017;82:31–40.
Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, Gizinski A, Yalavarthi S, Knight JS, et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci Transl Med. 2013;5:178ra40.
Sur Chowdhury C, Giaglis S, Walker UA, Buser A, Hahn S, Hasler P. Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: analysis of underlying signal transduction pathways and potential diagnostic utility. Arthritis Res Ther. 2014;16:R122.
Spengler J, Lugonja B, Ytterberg AJ, Zubarev RA, Creese AJ, Pearson MJ, et al. Release of Active Peptidyl Arginine Deiminases by Neutrophils Can Explain Production of Extracellular Citrullinated Autoantigens in Rheumatoid Arthritis Synovial Fluid. Arthritis Rheumatol. 2015;67:3135–45.
Fert-Bober J, Darrah E, Andrade F. Insights into the study and origin of the citrullinome in rheumatoid arthritis. Immunol Rev. 2020;294:133–47.
Chirivi RGS, van Rosmalen JWG, van der Linden M, Euler M, Schmets G, Bogatkevich G, et al. Therapeutic ACPA inhibits NET formation: a potential therapy for neutrophil-mediated inflammatory diseases. Cell Mol Immunol. 2021;18:1528–44.
Carmona-Rivera C, Carlucci PM, Moore E, Lingampalli N, Uchtenhagen H, James E, et al. Synovial fibroblast-neutrophil interactions promote pathogenic adaptive immunity in rheumatoid arthritis. Sci Immunol. 2017;2:eaag3358.
Tang J, Xia J, Gao H, Jiang R, Xiao L, Sheng H, et al. IL33-induced neutrophil extracellular traps (NETs) mediate a positive feedback loop for synovial inflammation and NET amplification in rheumatoid arthritis. Exp Mol Med. 2024;56:2602–16.
Wilson AS, Randall KL, Pettitt JA, Ellyard JI, Blumenthal A, Enders A, et al. Neutrophil extracellular traps and their histones promote Th17 cell differentiation directly via TLR2. Nat Commun. 2022;13:528.
Karmakar U, Vermeren S. Crosstalk between B cells and neutrophils in rheumatoid arthritis. Immunology. 2021;164:689–700.
Curran AM, Girgis AA, Jang Y, Crawford JD, Thomas MA, Kawalerski R, et al. Citrullination modulates antigen processing and presentation by revealing cryptic epitopes in rheumatoid arthritis. Nat Commun. 2023;14:1061.
Chen X, Du R, Wang P, Qiu W, Chen L, Wan J, et al. Proteomic analysis of infiltrating neutrophils from rheumatoid arthritis synovial fluid and their contribution to protein carbamylation. Front Immunol. 2025;16:1563426.
O’Neil LJ, Oliveira CB, Wang X, Navarrete M, Barrera-Vargas A, Merayo-Chalico J, et al. Neutrophil extracellular trap-associated carbamylation and histones trigger osteoclast formation in rheumatoid arthritis. Ann Rheum Dis. 2023;82:630–8.
Malamud M, Whitehead L, McIntosh A, Colella F, Roelofs AJ, Kusakabe T, et al. Recognition and control of neutrophil extracellular trap formation by MICL. Nature. 2024;633:442–50.
Schneider AH, Taira TM, Públio GA, da Silva Prado D, Donate Yabuta PB, Dos Santos JC, et al. Neutrophil extracellular traps mediate bone erosion in rheumatoid arthritis by enhancing RANKL-induced osteoclastogenesis. Br J Pharm. 2024;181:429–46.
Zhao J, Liu Y, Shi X, Dang J, Liu Y, Li S, et al. Infusion of GMSCs relieves autoimmune arthritis by suppressing the externalization of neutrophil extracellular traps via PGE2-PKA-ERK axis. J Adv Res. 2024;58:79–91.
Dang PM-C, Stensballe A, Boussetta T, Raad H, Dewas C, Kroviarski Y, et al. A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites. J Clin Invest. 2006;116:2033–43.
Liao Y-C, Wu S-Y, Huang Y-F, Lo P-C, Chan T-Y, Chen C-A, et al. NOX2-Deficient Neutrophils Facilitate Joint Inflammation Through Higher Pro-Inflammatory and Weakened Immune Checkpoint Activities. Front Immunol. 2021;12:743030.
Chen T, Zhou Z, Liu Y, Xu J, Zhu C, Sun R, et al. Neutrophils with low production of reactive oxygen species are activated during immune priming and promote development of arthritis. Redox Biol. 2024;78:103401.
Wright HL, Chikura B, Bucknall RC, Moots RJ, Edwards SW. Changes in expression of membrane TNF, NF-{kappa}B activation and neutrophil apoptosis during active and resolved inflammation. Ann Rheum Dis. 2011;70:537–43.
Wright HL, Bucknall RC, Moots RJ, Edwards SW. Analysis of SF and plasma cytokines provides insights into the mechanisms of inflammatory arthritis and may predict response to therapy. Rheumatology. 2012;51:451–9.
Parsonage G, Filer A, Bik M, Hardie D, Lax S, Howlett K, et al. Prolonged, granulocyte-macrophage colony-stimulating factor dependent, neutrophil survival following rheumatoid synovial fibroblast activation by IL-17 and TNFalpha. Arthritis Res Ther. 2008;10:R47.
Watson RW, Rotstein OD, Parodo J, Bitar R, Marshall JC. The IL-1 beta-converting enzyme (caspase-1) inhibits apoptosis of inflammatory neutrophils through activation of IL-1 beta. J Immunol. 1998;161:957–62.
Ottonello L, Frumento G, Arduino N, Bertolotto M, Mancini M, Sottofattori E, et al. Delayed neutrophil apoptosis induced by synovial fluid in rheumatoid arthritis: role of cytokines, estrogens, and adenosine. Ann N Y Acad Sci. 2002;966:226–31.
Wong SH, Francis N, Chahal H, Raza K, Salmon M, Scheel-Toellner D, et al. Lactoferrin is a survival factor for neutrophils in rheumatoid synovial fluid. Rheumatology. 2009;48:39–44.
Cross A, Barnes T, Bucknall RC, Edwards SW, Moots RJ. Neutrophil apoptosis in rheumatoid arthritis is regulated by local oxygen tensions within joints. J Leukoc Biol. 2006;80:521–8.
Walmsley SR, Print C, Farahi N, Peyssonnaux C, Johnson RS, Cramer T, et al. Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity. J Exp Med. 2005;201:105–15.
Elks PM, van Eeden FJ, Dixon G, Wang X, Reyes-Aldasoro CC, Ingham PW, et al. Activation of hypoxia-inducible factor-1α (Hif-1α) delays inflammation resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish inflammation model. Blood. 2011;118:712–22.
Gao L, He C, Yang A, Zhou H, Lu Q, Birge RB, et al. Receptor tyrosine kinases Tyro3, Axl, and Mertk differentially contribute to antibody-induced arthritis. Cell Commun Signal. 2023;21:195.
Schneider K, Arandjelovic S. Apoptotic cell clearance components in inflammatory arthritis. Immunol Rev. 2023;319:142–50.
Arandjelovic S, Perry JSA, Lucas CD, Penberthy KK, Kim T-H, Zhou M, et al. A noncanonical role for the engulfment gene ELMO1 in neutrophils that promotes inflammatory arthritis. Nat Immunol. 2019;20:141–51.
Xie MM, Dai B, Hackney JA, Sun T, Zhang J, Jackman JK, et al. An agonistic anti-signal regulatory protein α antibody for chronic inflammatory diseases. Cell Rep Med. 2023;4:101130.
Liu Y, Luo X, Chen Y, Dang J, Zeng D, Guo X, et al. Heterogeneous ferroptosis susceptibility of macrophages caused by focal iron overload exacerbates rheumatoid arthritis. Redox Biol. 2024;69:103008.
Liu Y, Liang J, Sha Z, Yang C. Inhibition of Oxidative Stress-Induced Ferroptosis Can Alleviate Rheumatoid Arthritis in Human. J Immunol Res. 2024;2024:9943747.
Zhang Y, Huang X, Qi B, Sun C, Sun K, Liu N, et al. Ferroptosis and musculoskeletal diseases: ‘Iron Maiden’ cell death may be a promising therapeutic target. Front Immunol. 2022;13:972753.
Zhao H, Dong Q, Hua H, Wu H, Ao L. Contemporary insights and prospects on ferroptosis in rheumatoid arthritis management. Front Immunol. 2024;15:1455607.
Wang X, Gessier F, Perozzo R, Stojkov D, Hosseini A, Amirshahrokhi K, et al. RIPK3-MLKL-Mediated Neutrophil Death Requires Concurrent Activation of Fibroblast Activation Protein-α. J Immunol. 2020;205:1653–63.
Lee SH, Kwon JY, Kim S-Y, Jung K, Cho M-L. Interferon-gamma regulates inflammatory cell death by targeting necroptosis in experimental autoimmune arthritis. Sci Rep. 2017;7:10133.
Mathews RJ, Robinson JI, Battellino M, Wong C, Taylor JC. Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS) et al. Evidence of NLRP3-inflammasome activation in rheumatoid arthritis (RA); genetic variants within the NLRP3-inflammasome complex in relation to susceptibility to RA and response to anti-TNF treatment. Ann Rheum Dis. 2014;73:1202–10.
Yang Z, Cao J, Yu C, Yang Q, Zhang Y, Han L. Caspase-1 mediated interleukin-18 activation in neutrophils promotes the activity of rheumatoid arthritis in a NLRP3 inflammasome independent manner. Jt Bone Spine. 2016;83:282–9.
Choulaki C, Papadaki G, Repa A, Kampouraki E, Kambas K, Ritis K, et al. Enhanced activity of NLRP3 inflammasome in peripheral blood cells of patients with active rheumatoid arthritis. Arthritis Res Ther. 2015;17:257.
Wyman TH, Dinarello CA, Banerjee A, Gamboni-Robertson F, Hiester AA, England KM, et al. Physiological levels of interleukin-18 stimulate multiple neutrophil functions through p38 MAP kinase activation. J Leukoc Biol. 2002;72:401–9.
Chen Y-M, Chang C-Y, Chen H-H, Hsieh C-W, Tang K-T, Yang M-C, et al. Association between autophagy and inflammation in patients with rheumatoid arthritis receiving biologic therapy. Arthritis Res Ther. 2018;20:268.
An Q, Yan W, Zhao Y, Yu K. Enhanced neutrophil autophagy and increased concentrations of IL-6, IL-8, IL-10 and MCP-1 in rheumatoid arthritis. Int Immunopharmacol. 2018;65:119–28.
Vaduganathan M, Mensah GA, Turco JV, Fuster V, Roth GA. The Global Burden of Cardiovascular Diseases and Risk: A Compass for Future Health. J Am Coll Cardiol. 2022;80:2361–71.
Zhang Q, Ding X, Xu Y, Lin Y, Wu Y. Neutrophil-mediated effects of S100A12 on major adverse cardiovascular events: Insights from the UK biobank. Am J Prev Cardiol. 2025;23:101278.
Steinberg D. The LDL modification hypothesis of atherogenesis: an update. J Lipid Res. 2009;50:S376–81.
Domínguez-Luis MJ, Armas-González E, Herrera-García A, Arce-Franco M, Feria M, Vicente-Manzanares M, et al. L-selectin expression is regulated by CXCL8-induced reactive oxygen species produced during human neutrophil rolling. Eur J Immunol. 2019;49:386–97.
Drechsler M, Megens RTA, van Zandvoort M, Weber C, Soehnlein O. Hyperlipidemia-triggered neutrophilia promotes early atherosclerosis. Circulation. 2010;122:1837–45.
Rotzius P, Thams S, Soehnlein O, Kenne E, Tseng C-N, Björkström NK, et al. Distinct infiltration of neutrophils in lesion shoulders in ApoE−/− mice. Am J Pathol. 2010;177:493–500.
Ionita MG, van den Borne P, Catanzariti LM, Moll FL, de Vries J-PPM, Pasterkamp G, et al. High neutrophil numbers in human carotid atherosclerotic plaques are associated with characteristics of rupture-prone lesions. Arterioscler Thromb Vasc Biol. 2010;30:1842–8.
Letian A, Young K, Pi A, Gonzatti M, Volk R, Sharma I et al. Neutrophil TLR2 signaling promotes lipid accumulation and vascular plaque growth. bioRxiv. 2025. https://www.biorxiv.org/content/10.1101/2025.07.09.663961v1.
Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest. 1994;94:2493–503.
Megens RTA, Vijayan S, Lievens D, Döring Y, van Zandvoort MAMJ, Grommes J, et al. Presence of luminal neutrophil extracellular traps in atherosclerosis. Thromb Hemost. 2012;107:597–8.
Baratchi S, Danish H, Chheang C, Zhou Y, Huang A, Lai A, et al. Piezo1 expression in neutrophils regulates shear-induced NETosis. Nat Commun. 2024;15:7023.
Dhawan UK, Vartak T, Englert H, Russo S, Vasconcellos LRC, Singhal A et al. Macrophage DNases Limit Neutrophil Extracellular Trap-Mediated Defective Efferocytosis in Atherosclerosis. Circ Res. 2025;137:1255–57.
Yalcinkaya M, Fotakis P, Liu W, Endo-Umeda K, Dou H, Abramowicz S, et al. Cholesterol accumulation in macrophages drives NETosis in atherosclerotic plaques via IL-1β secretion. Cardiovasc Res. 2023;119:969–81.
Pertiwi KR, van der Wal AC, Pabittei DR, Mackaaij C, van Leeuwen MB, Li X, et al. Neutrophil Extracellular Traps Participate in All Different Types of Thrombotic and Hemorrhagic Complications of Coronary Atherosclerosis. Thromb Hemost. 2018;118:1078–87.
Zhai M, Gong S, Luan P, Shi Y, Kou W, Zeng Y, et al. Extracellular traps from activated vascular smooth muscle cells drive the progression of atherosclerosis. Nat Commun. 2022;13:7500.
Danne C, Skerniskyte J, Marteyn B, Sokol H. Neutrophils: from IBD to the gut microbiota. Nat Rev Gastroenterol Hepatol. 2024;21:184–97.
Wang S, Song R, Wang Z, Jing Z, Wang S, Ma J. S100A8/A9 in Inflammation. Front Immunol. 2018;9:1298.
Edgeworth J, Gorman M, Bennett R, Freemont P, Hogg N. Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells. J Biol Chem. 1991;266:7706–13.
Amamou A, Leboutte M, Breton J, Ribet D, Thiebaut P-A, Bôle-Feysot C, et al. Mineralocorticoid receptor activation contributes to intestinal fibrosis through neutrophil gelatinase-associated lipocalin in preclinical models. Nat Commun. 2025;16:6318.
Thorsvik S, Bakke I, van Beelen Granlund A, Røyset ES, Damås JK, Østvik AE, et al. Expression of neutrophil gelatinase-associated lipocalin (NGAL) in the gut in Crohn’s disease. Cell Tissue Res. 2018;374:339–48.
Kruidenier L, Kuiper I, Lamers CBHW, Verspaget HW. Intestinal oxidative damage in inflammatory bowel disease: semiquantification, localization, and association with mucosal antioxidants. J Pathol. 2003;201:28–36.
Abd El Hafez A, Mohamed AS, Shehta A, Sheta HAEAS. Neutrophil extracellular traps-associated protein peptidyl arginine deaminase 4 immunohistochemical expression in ulcerative colitis and its association with the prognostic predictors. Pathol Res Pr. 2020;216:153102.
Wang S, Song Y, Wang Z, Chang X, Wu H, Yan Z, et al. Neutrophil-derived PAD4 induces citrullination of CKMT1 exacerbates mucosal inflammation in inflammatory bowel disease. Cell Mol Immunol. 2024;21:620–33.
Borichevsky GM, Swaminathan A, Smith BR, Edwards TS, Ashby LV, Frampton CMA et al. Myeloperoxidase Enzyme Activity in Feces Reflects Endoscopic Severity in Inflammatory Bowel Disease. Inflamm Bowel Dis 2025;31:2254–68.
Liu C, Mo L-H, Feng B-S, Jin Q-R, Li Y, Lin J, et al. Twist1 contributes to developing and sustaining corticosteroid resistance in ulcerative colitis. Theranostics. 2021;11:7797–812.
Friedrich M, Pohin M, Jackson MA, Korsunsky I, Bullers SJ, Rue-Albrecht K, et al. IL-1-driven stromal-neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies. Nat Med. 2021;27:1970–81.
West NR, Hegazy AN, Owens BMJ, Bullers SJ, Linggi B, Buonocore S, et al. Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease. Nat Med. 2017;23:579–89.
Grenier A, Dehoux M, Boutten A, Arce-Vicioso M, Durand G, Gougerot-Pocidalo MA, et al. Oncostatin M production and regulation by human polymorphonuclear neutrophils. Blood. 1999;93:1413–21.
Kühl AA, Kakirman H, Janotta M, Dreher S, Cremer P, Pawlowski NN, et al. Aggravation of different types of experimental colitis by depletion or adhesion blockade of neutrophils. Gastroenterology. 2007;133:1882–92.
Zhou G, Yu L, Fang L, Yang W, Yu T, Miao Y, et al. CD177+ neutrophils as functionally activated neutrophils negatively regulate IBD. Gut. 2018;67:1052–63.
Mills KHG. IL-17 and IL-17-producing cells in protection versus pathology. Nat Rev Immunol. 2023;23:38–54.
Taylor PR, Roy S, Leal SM, Sun Y, Howell SJ, Cobb BA, et al. Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORγt and dectin-2. Nat Immunol. 2014;15:143–51.
Tamassia N, Arruda-Silva F, Calzetti F, Lonardi S, Gasperini S, Gardiman E, et al. A Reappraisal on the Potential Ability of Human Neutrophils to Express and Produce IL-17 Family Members In Vitro: Failure to Reproducibly Detect It. Front Immunol. 2018;9:795.
Gonzalez-Orozco M, Barbosa-Cobos RE, Santana-Sanchez P, Becerril-Mendoza L, Limon-Camacho L, Juarez-Estrada AI, et al. Endogenous stimulation is responsible for the high frequency of IL-17A-producing neutrophils in patients with rheumatoid arthritis. Allergy Asthma Clin Immunol. 2019;15:44.
Li J, Shi W, Sun H, Ji Y, Chen Y, Guo X, et al. Activation of DR3 signaling causes loss of ILC3s and exacerbates intestinal inflammation. Nat Commun. 2019;10:3371.
Zhang D, Frenette PS. Cross talk between neutrophils and the microbiota. Blood. 2019;133:2168–77.
Duvallet C, Gibbons SM, Gurry T, Irizarry RA, Alm EJ. Meta-analysis of gut microbiome studies identifies disease-specific and shared responses. Nat Commun. 2017;8:1784.
Mukhopadhya I, Louis P. Gut microbiota-derived short-chain fatty acids and their role in human health and disease. Nat Rev Microbiol. 2025;23:635–51.
Vinolo MAR, Rodrigues HG, Hatanaka E, Sato FT, Sampaio SC, Curi R. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J Nutr Biochem. 2011;22:849–55.
Ji J, Shu D, Zheng M, Wang J, Luo C, Wang Y, et al. Microbial metabolite butyrate facilitates M2 macrophage polarization and function. Sci Rep. 2016;6:24838.
Li G, Lin J, Zhang C, Gao H, Lu H, Gao X, et al. Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease. Gut Microbes. 2021;13:1968257.
Dai X, Fan Y, Zhao X. Systemic lupus erythematosus: updated insights on the pathogenesis, diagnosis, prevention and therapeutics. Sign Transduct Target Ther. 2025;10:102.
Tay SH, Celhar T, Fairhurst A-M. Low-Density Neutrophils in Systemic Lupus Erythematosus. Arthritis Rheumatol. 2020;72:1587–95.
Kaplan MJ. Exploring the Role of Neutrophil Extracellular Traps in Systemic Lupus Erythematosus: A Clinical Case Study and Comprehensive Review. Arthritis Rheumatol. 2025;77:247–52.
Zeng Y, Xu W, Chao P, Xiao Y, Yang T. Neutrophil extracellular traps as a potential marker of systemic lupus erythematosus activity. Int Immunopharmacol. 2025;146:113840.
Liu L, de Leeuw K, van Goor H, Doornbos-van der Meer B, Arends S, Westra J. Neutrophil extracellular traps and oxidative stress in systemic lupus erythematosus patients with and without renal involvement. Arthritis Res Ther. 2024;26:220.
Li H, Zhang X, Shang J, Feng X, Yu L, Fan J, et al. Identification of NETs-related biomarkers and molecular clusters in systemic lupus erythematosus. Front Immunol. 2023;14:1150828.
Wang T, Kuley R, Hermanson P, Chu P, Pohlmeyer C, Ravichandar JD, et al. Immune complexes-mediated activation of neutrophils in systemic lupus erythematosus is dependent on RNA recognition by toll-like receptor 8. Front Immunol. 2024;15:1515469.
Tay SH, Zharkova O, Lee HY, Toh MMX, Libau EA, Celhar T, et al. Platelet TLR7 is essential for the formation of platelet-neutrophil complexes and low-density neutrophils in lupus nephritis. Rheumatology. 2024;63:551–62.
Jog NR, Wagner CA, Aberle T, Chakravarty EF, Arriens C, Guthridge JM, et al. Neutrophils isolated from systemic lupus erythematosus patients exhibit a distinct functional phenotype. Front Immunol. 2024;15:1339250.
Wigerblad G, Kaplan MJ. Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases. Nat Rev Immunol. 2023;23:274–88.
Fan X, Ng CT, Guo D, Lim F, Tan JC, Law A, et al. Dampened Inflammation and Improved Survival After CXCL5 Administration in Murine Lupus via Myeloid and Neutrophil Pathways. Arthritis Rheumatol. 2023;75:553–66.
Shingu M, Oribe M, Todoroki T, Tatsukawa K, Tomo-oka K, Yasuda M, et al. Serum factors from patients with systemic lupus erythematosus enhancing superoxide generation by normal neutrophils. J Invest Dermatol. 1983;81:212–5.
Alves CMOS, Marzocchi-Machado CM, Louzada-Junior P, Azzolini AECS, Polizello ACM, de Carvalho IF, et al. Superoxide anion production by neutrophils is associated with prevalent clinical manifestations in systemic lupus erythematosus. Clin Rheumatol. 2008;27:701–8.
Nishi H, Furuhashi K, Cullere X, Saggu G, Miller MJ, Chen Y, et al. Neutrophil FcγRIIA promotes IgG-mediated glomerular neutrophil capture via Abl/Src kinases. J Clin Invest. 2017;127:3810–26.
Flores-Mendoza G, Sansón SP, Rodríguez-Castro S, Crispín JC, Rosetti F. Mechanisms of Tissue Injury in Lupus Nephritis. Trends Mol Med. 2018;24:364–78.
Yan Z, Chen Q, Xia Y. Oxidative Stress Contributes to Inflammatory and Cellular Damage in Systemic Lupus Erythematosus: Cellular Markers and Molecular Mechanism. J Inflamm Res. 2023;16:453–65.
Jiang X, Xiao X, Li H, Gong Y, Wang M, Yang H, et al. Oxidized galectin-1 in SLE fails to bind the inhibitory receptor VSTM1 and increases reactive oxygen species levels in neutrophils. Cell Mol Immunol. 2023;20:1339–51.
Kelkka T, Kienhöfer D, Hoffmann M, Linja M, Wing K, Sareila O, et al. Reactive oxygen species deficiency induces autoimmunity with type 1 interferon signature. Antioxid Redox Signal. 2014;21:2231–45.
Olsson LM, Johansson ÅC, Gullstrand B, Jönsen A, Saevarsdottir S, Rönnblom L, et al. A single-nucleotide polymorphism in the NCF1 gene leading to reduced oxidative burst is associated with systemic lupus erythematosus. Ann Rheum Dis. 2017;76:1607–13.
Zhao H, Lin Z, Zhang P, Rao J, Xu S, Luo Q, et al. KLF2 controls the apoptosis of neutrophils and is associated with disease activity of systemic lupus erythematosus. Arthritis Res Ther. 2024;26:222.
Guo X, Fang X, He G, Zaman MH, Fei X, Qiao W, et al. The role of neutrophils in skin damage induced by tissue-deposited lupus IgG. Immunology. 2018;154:604–12.
Midgley A, Beresford MW. Cellular localization of nuclear antigens during neutrophil apoptosis: mechanism for autoantigen exposure?. Lupus. 2011;20:641–6.
Midgley A, Thorbinson C, Beresford MW. Expression of Toll-like receptors and their detection of nuclear self-antigens lead to immune activation in JSLE. Rheumatology. 2012;51:824–32.
Mahajan A, Herrmann M, Muñoz LE. Clearance Deficiency and Cell Death Pathways: A Model for the Pathogenesis of SLE. Front Immunol. 2016;7:35.
Rother N, Pieterse E, Lubbers J, Hilbrands L, van der Vlag J. Acetylated Histones in Apoptotic Microparticles Drive the Formation of Neutrophil Extracellular Traps in Active Lupus Nephritis. Front Immunol. 2017;8:1136.
Dieker J, Tel J, Pieterse E, Thielen A, Rother N, Bakker M, et al. Circulating Apoptotic Microparticles in Systemic Lupus Erythematosus Patients Drive the Activation of Dendritic Cell Subsets and Prime Neutrophils for NETosis. Arthritis Rheumatol. 2016;68:462–72.
Miao N, Wang Z, Wang Q, Xie H, Yang N, Wang Y, et al. Oxidized mitochondrial DNA induces gasdermin D oligomerization in systemic lupus erythematosus. Nat Commun. 2023;14:872.
Li P, Jiang M, Li K, Li H, Zhou Y, Xiao X, et al. Glutathione peroxidase 4-regulated neutrophil ferroptosis induces systemic autoimmunity. Nat Immunol. 2021;22:1107–17.
Baker T, Sharifian H, Newcombe PJ, Gavin PG, Lazarus MN, Ramaswamy M, et al. Type I interferon blockade with anifrolumab in patients with systemic lupus erythematosus modulates key immunopathological pathways in a gene expression and proteomic analysis of two phase 3 trials. Ann Rheum Dis. 2024;83:1018–27.
Moysidou G-S, Garantziotis P, Sentis G, Nikoleri D, Malissovas N, Nikoloudaki M, et al. Molecular basis for the disease-modifying effects of belimumab in systemic lupus erythematosus and molecular predictors of early response: blood transcriptome analysis implicates the innate immunity and DNA damage response pathways. Ann Rheum Dis. 2025;84:262–73.
Ou Q, Niu L, Wang D, Yao G, Ren Q, Li Z, et al. Mesenchymal stromal cells induce neutrophil aggregation and extracellular vesicle storms for systemic lupus erythematosus. Sig Transduct Target Ther. 2025;10:344.
Christenson SA, Smith BM, Bafadhel M, Putcha N. Chronic obstructive pulmonary disease. Lancet. 2022;399:2227–42.
Agustí A, Hogg JC. Update on the Pathogenesis of Chronic Obstructive Pulmonary Disease. N Engl J Med. 2019;381:1248–56.
Richens TR, Linderman DJ, Horstmann SA, Lambert C, Xiao Y-Q, Keith RL, et al. Cigarette smoke impairs clearance of apoptotic cells through oxidant-dependent activation of RhoA. Am J Respir Crit Care Med. 2009;179:1011–21.
Hao W, Li M, Zhang Y, Zhang C, Xue Y. Expressions of MMP-12, TIMP-4, and Neutrophil Elastase in PBMCs and Exhaled Breath Condensate in Patients with COPD and Their Relationships with Disease Severity and Acute Exacerbations. J Immunol Res. 2019;2019:7142438.
Stănescu D, Sanna A, Veriter C, Kostianev S, Calcagni PG, Fabbri LM, et al. Airways obstruction, chronic expectoration, and rapid decline of FEV1 in smokers are associated with increased levels of sputum neutrophils. Thorax. 1996;51:267–71.
Mallia-Milanes B, Dufour A, Philp C, Solis N, Klein T, Fischer M, et al. TAILS proteomics reveals dynamic changes in airway proteolysis controlling protease activity and innate immunity during COPD exacerbations. Am J Physiol Lung Cell Mol Physiol. 2018;315:L1003–L1014.
Fujimoto K, Yasuo M, Urushibata K, Hanaoka M, Koizumi T, Kubo K. Airway inflammation during stable and acutely exacerbated chronic obstructive pulmonary disease. Eur Respir J. 2005;25:640–6.
Dicker AJ, Crichton ML, Pumphrey EG, Cassidy AJ, Suarez-Cuartin G, Sibila O, et al. Neutrophil extracellular traps are associated with disease severity and microbiota diversity in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2018;141:117–27.
Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P, et al. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med. 2011;184:662–71.
Calverley PMA, Sethi S, Dawson M, Ward CK, Finch DK, Penney M, et al. A randomized, placebo-controlled trial of anti-interleukin-1 receptor 1 monoclonal antibody MEDI8968 in chronic obstructive pulmonary disease. Respir Res. 2017;18:153.
Mahler DA, Huang S, Tabrizi M, Bell GM. Efficacy and safety of a monoclonal antibody recognizing interleukin-8 in COPD: a pilot study. Chest. 2004;126:926–34.
Kuna P, Jenkins M, O’Brien CD, Fahy WA. AZD9668, a neutrophil elastase inhibitor, plus ongoing budesonide/formoterol in patients with COPD. Respir Med. 2012;106:531–9.
Chalmers JD, Burgel P-R, Daley CL, De Soyza A, Haworth CS, Mauger D, et al. Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis. N Engl J Med. 2025;392:1569–81.
Tavares LP, Negreiros-Lima GL, Lima KM, E Silva PMR, Pinho V, Teixeira MM, et al. Blame the signaling: Role of cAMP for the resolution of inflammation. Pharm Res. 2020;159:105030.
Rabe KF, Calverley PMA, Martinez FJ, Fabbri LM. Effect of roflumilast in patients with severe COPD and a history of hospitalization. Eur Respir J. 2017;50:1700158.
Martinez FJ, Calverley PMA, Goehring U-M, Brose M, Fabbri LM, Rabe KF. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicenter randomized controlled trial. Lancet. 2015;385:857–66.
Martinez FJ, Rabe KF, Sethi S, Pizzichini E, McIvor A, Anzueto A, et al. Effect of Roflumilast and Inhaled Corticosteroid/Long-Acting β2-Agonist on Chronic Obstructive Pulmonary Disease Exacerbations (RE(2)SPOND). A Randomized Clinical Trial. Am J Respir Crit Care Med. 2016;194:559–67.
Vlahos R, Bozinovski S, Jones JE, Powell J, Gras J, Lilja A, et al. Differential protease, innate immunity, and NF-kappaB induction profiles during lung inflammation induced by subchronic cigarette smoke exposure in mice. Am J Physiol Lung Cell Mol Physiol. 2006;290:L931–45.
Dimic-Janjic S, Hoda MA, Milenkovic B, Kotur-Stevuljevic J, Stjepanovic M, Gompelmann D, et al. The usefulness of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio for diagnosis and assessment of COPD severity. Eur J Med Res. 2023;28:127.
Linder R, Rönmark E, Pourazar J, Behndig A, Blomberg A, Lindberg A. Serum metalloproteinase-9 is related to COPD severity and symptoms – cross-sectional data from a population based cohort-study. Respir Res. 2015;16:28.
Brajer B, Batura-Gabryel H, Nowicka A, Kuznar-Kaminska B, Szczepanik A. Concentration of matrix metalloproteinase-9 in serum of patients with chronic obstructive pulmonary disease and a degree of airway obstruction and disease progression. J Physiol Pharm. 2008;59:145–52.
Wang K, Liao Y, Li X, Wang R, Zeng Z, Cheng M, et al. Inhibition of neutrophil elastase prevents cigarette smoke exposure-induced formation of neutrophil extracellular traps and improves lung function in a mouse model of chronic obstructive pulmonary disease. Int Immunopharmacol. 2023;114:109537.
Katsoulis O, Toussaint M, Jackson MM, Mallia P, Footitt J, Mincham KT, et al. Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations. Nat Commun. 2024;15:5766.
Chen J, Wang T, Li X, Gao L, Wang K, Cheng M, et al. DNA of neutrophil extracellular traps promote NF-κB-dependent autoimmunity via cGAS/TLR9 in chronic obstructive pulmonary disease. Signal Transduct Target Ther. 2024;9:163.
Benjamin JT, Plosa EJ, Sucre JM, van der Meer R, Dave S, Gutor S, et al. Neutrophilic inflammation during lung development disrupts elastin assembly and predisposes adult mice to COPD. J Clin Invest. 2021;131:e139481.
Hara A, Sakamoto N, Ishimatsu Y, Kakugawa T, Nakashima S, Hara S, et al. S100A9 in BALF is a candidate biomarker of idiopathic pulmonary fibrosis. Respir Med. 2012;106:571–80.
Crowley LE, Stockley RA, Thickett DR, Dosanjh D, Scott A, Parekh D. Neutrophil dynamics in pulmonary fibrosis: pathophysiological and therapeutic perspectives. Eur Respir Rev. 2024;33:240139.
Ziegenhagen MW, Zabel P, Zissel G, Schlaak M, Müller-Quernheim J. Serum level of interleukin 8 is elevated in idiopathic pulmonary fibrosis and indicates disease activity. Am J Respir Crit Care Med. 1998;157:762–8.
Richards TJ, Kaminski N, Baribaud F, Flavin S, Brodmerkel C, Horowitz D, et al. Peripheral blood proteins predict mortality in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2012;185:67–76.
Dunbar A, Lu M, Farina M, Park Y, Yang J, Kim D, et al. Increased Interleukin-8 (IL8)-CXCR2 Signaling Promotes Progression of Bone Marrow Fibrosis in Myeloproliferative Neoplasms. Blood. 2020;136:6–7.
Nishimoto-Kakiuchi A, Sato I, Nakano K, Ohmori H, Kayukawa Y, Tanimura H, et al. A long-acting anti-IL-8 antibody improves inflammation and fibrosis in endometriosis. Sci Transl Med. 2023;15:eabq5858.
Vermeersch G, Proost P, Struyf S, Gouwy M, Devos T. CXCL8 and its cognate receptors CXCR1/CXCR2 in primary myelofibrosis. Hematologica. 2024;109:2060–72.
Chrysanthopoulou A, Mitroulis I, Apostolidou E, Arelaki S, Mikroulis D, Konstantinidis T, et al. Neutrophil extracellular traps promote differentiation and function of fibroblasts. J Pathol. 2014;233:294–307.
Gregory AD, Kliment CR, Metz HE, Kim K-H, Kargl J, Agostini BA, et al. Neutrophil elastase promotes myofibroblast differentiation in lung fibrosis. J Leukoc Biol. 2015;98:143–52.
Yamanouchi H, Fujita J, Hojo S, Yoshinouchi T, Kamei T, Yamadori I, et al. Neutrophil elastase: alpha-1-proteinase inhibitor complex in serum and bronchoalveolar lavage fluid in patients with pulmonary fibrosis. Eur Respir J. 1998;11:120–5.
Khawaja AA, Chong DLW, Sahota J, Mikolasch TA, Pericleous C, Ripoll VM, et al. Identification of a Novel HIF-1α-αMβ2 Integrin-NET Axis in Fibrotic Interstitial Lung Disease. Front Immunol. 2020;11:2190.
Younesi FS, Miller AE, Barker TH, Rossi FMV, Hinz B. Fibroblast and myofibroblast activation in normal tissue repair and fibrosis. Nat Rev Mol Cell Biol. 2024;25:617–38.
Zhang X, Zhang Y, Liu Y. Fibroblast activation and heterogeneity in fibrotic disease. Nat Rev Nephrol. 2025;21:613–32.
Zhang YE. Non-Smad Signaling Pathways of the TGF-β Family. Cold Spring Harb Perspect Biol. 2017;9:a022129.
Takemasa A, Ishii Y, Fukuda T. A neutrophil elastase inhibitor prevents bleomycin-induced pulmonary fibrosis in mice. Eur Respir J. 2012;40:1475–82.
Kobayashi T, Kim H, Liu X, Sugiura H, Kohyama T, Fang Q, et al. Matrix metalloproteinase-9 activates TGF-β and stimulates fibroblast contraction of collagen gels. Am J Physiol Lung Cell Mol Physiol. 2014;306:L1006–1015.
Jobling MF, Mott JD, Finnegan MT, Jurukovski V, Erickson AC, Walian PJ, et al. Isoform-specific activation of latent transforming growth factor beta (LTGF-beta) by reactive oxygen species. Radiat Res. 2006;166:839–48.
Selige J, Hatzelmann A, Dunkern T. The differential impact of PDE4 subtypes in human lung fibroblasts on cytokine-induced proliferation and myofibroblast conversion. J Cell Physiol. 2011;226:1970–80.
de Castro Brás LE, Frangogiannis NG. Extracellular matrix-derived peptides in tissue remodeling and fibrosis. Matrix Biol. 2020;91–92:176–87.
Dayer C, Stamenkovic I. Recruitment of Matrix Metalloproteinase-9 (MMP-9) to the Fibroblast Cell Surface by Lysyl Hydroxylase 3 (LH3) Triggers Transforming Growth Factor-β (TGF-β) Activation and Fibroblast Differentiation. J Biol Chem. 2015;290:13763–78.
Vandooren J, Swinnen W, Ugarte-Berzal E, Boon L, Dorst D, Martens E, et al. Endotoxemia shifts neutrophils with TIMP-free gelatinase B/MMP-9 from bone marrow to the periphery and induces systematic upregulation of TIMP-1. Hematologica. 2017;102:1671–82.
Okamoto T, Akaike T, Sawa T, Miyamoto Y, van der Vliet A, Maeda H. Activation of matrix metalloproteinases by peroxynitrite-induced protein S-glutathiolation via disulfide S-oxide formation. J Biol Chem. 2001;276:29596–602.
Murphy G. Tissue inhibitors of metalloproteinases. Genome Biol. 2011;12:233.
Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, et al. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol. 2000;2:737–44.
Ebina M, Shimizukawa M, Shibata N, Kimura Y, Suzuki T, Endo M, et al. Heterogeneous increase in CD34-positive alveolar capillaries in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2004;169:1203–8.
Liu L, You Z, Yu H, Zhou L, Zhao H, Yan X, et al. Mechanotransduction-modulated fibrotic microniches reveal the contribution of angiogenesis in liver fibrosis. Nat Mater. 2017;16:1252–61.
Mesa RA, Hanson CA, Rajkumar SV, Schroeder G, Tefferi A. Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia. Blood. 2000;96:3374–80.
Gaggar A, Jackson PL, Noerager BD, O’Reilly PJ, McQuaid DB, Rowe SM, et al. A Novel Proteolytic Cascade Generates an Extracellular Matrix-Derived Chemoattractant in Chronic Neutrophilic Inflammation12. J Immunol. 2008;180:5662–9.
O’Reilly PJ, Jackson PL, Wells JM, Dransfield MT, Scanlon PD, Blalock JE. Sputum PGP is reduced by azithromycin treatment in patients with COPD and correlates with exacerbations. BMJ Open. 2013;3:e004140.
Verleden SE, Vandooren J, Vos R, Willems S, DuPont LJ, Verleden GM, et al. Azithromycin decreases MMP-9 expression in the airways of lung transplant recipients. Transpl Immunol. 2011;25:159–62.
Jaffar J, Unger S, Corte TJ, Keller M, Wolters PJ, Richeldi L, et al. Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis. Chest. 2014;146:1055–63.
Liu G, Cooley MA, Jarnicki AG, Hsu AC-Y, Nair PM, Haw TJ, et al. Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases. JCI Insight. 2016;1:e86380.
Ge Q, Chen L, Jaffar J, Argraves WS, Twal WO, Hansbro P, et al. Fibulin1C peptide induces cell attachment and extracellular matrix deposition in lung fibroblasts. Sci Rep. 2015;5:9496.
Liu G, Cooley MA, Jarnicki AG, Borghuis T, Nair PM, Tjin G, et al. Fibulin-1c regulates transforming growth factor-β activation in pulmonary tissue fibrosis. JCI Insight. 2019;5:e124529.
Tefferi A. Primary myelofibrosis: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023;98:801–21.
Luque Paz D, Kralovics R, Skoda RC. Genetic basis and molecular profiling in myeloproliferative neoplasms. Blood. 2023;141:1909–21.
Cominal JG, Cacemiro MdaC, Berzoti-Coelho MG, Pereira IEG, Frantz FG, Souto EX, et al. Bone Marrow Soluble Mediator Signatures of Patients With Philadelphia Chromosome-Negative Myeloproliferative Neoplasms. Front Oncol. 2021;11:665037.
Chen P, Wu B, Ji L, Zhan Y, Li F, Cheng L, et al. Cytokine Consistency Between Bone Marrow and Peripheral Blood in Patients With Philadelphia-Negative Myeloproliferative Neoplasms. Front Med. 2021;8:598182.
Fisher DAC, Fowles JS, Zhou A, Oh ST. Inflammatory Pathophysiology as a Contributor to Myeloproliferative Neoplasms. Front Immunol. 2021;12:683401.
Larsen MK, Skov V, Kjær L, Eickhardt-Dalbøge CS, Knudsen TA, Kristiansen MH, et al. Neutrophil-to-lymphocyte ratio and all-cause mortality with and without myeloproliferative neoplasms—a Danish longitudinal study. Blood Cancer J. 2024;14:1–12.
Vermeersch G, Gouwy M, Proost P, Struyf S, Devos T. Neutrophils in BCR::ABL1 negative MPN: Contributors or bystanders of fibrosis?. Blood Rev. 2025;72:101285.
Hurtado-Nedelec M, Csillag-Grange M-J, Boussetta T, Belambri SA, Fay M, Cassinat B, et al. Increased reactive oxygen species production and p47phox phosphorylation in neutrophils from myeloproliferative disorders patients with JAK2 (V617F) mutation. Hematologica. 2013;98:1517–24.
Liu R-M, Desai LP. Reciprocal regulation of TGF-β and reactive oxygen species: A perverse cycle for fibrosis. Redox Biol. 2015;6:565–77.
Xu M, Bruno E, Chao J, Huang S, Finazzi G, Fruchtman SM, et al. Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases. Blood. 2005;105:4508–15.
Lima LT, Nunes DPT, Gomes GW, Chauffaille MdeLLF, Silva MRR, Ponce CC, et al. Higher MMP9 and FGF2 Protein Levels and Elevated MMP9/TIMP Ratios Were Associated with JAK2V617F Mutation Regardless of Allele Burden in Myelofibrosis. Blood. 2014;124:5192.
Khatib-Massalha E, Di Buduo CA, Chédeville AL, Ho Y-H, Zhu Y, Grockowiak E, et al. Defective neutrophil clearance in JAK2V617F myeloproliferative neoplasms drives myelofibrosis via immune checkpoint CD24. Blood. 2025;146:717–31.
Arciprete F, Verachi P, Martelli F, Valeri M, Balliu M, Guglielmelli P, et al. Inhibition of CXCR1/2 reduces the emperipolesis between neutrophils and megakaryocytes in the Gata1low model of myelofibrosis. Exp Hematol. 2023;121:30–37.
Cunin P, Nigrovic PA. Megakaryocyte emperipolesis: a new frontier in cell-in-cell interaction. Platelets. 2020;31:700–6.
Schmitt A, Jouault H, Guichard J, Wendling F, Drouin A, Cramer EM. Pathologic interaction between megakaryocytes and polymorphonuclear leukocytes in myelofibrosis. Blood. 2000;96:1342–7.
Collinson RJ, Linden MD, Fuller KA, Wilson L, Mirzai B, Boey D, et al. Megakaryocyte emperipolesis in myeloproliferative neoplasms: Are neutrophils friends or foes?. J Leukoc Biol. 2025;117:qiaf093.
Cunin P, Bouslama R, Machlus KR, Martínez-Bonet M, Lee PY, Wactor A et al. Megakaryocyte emperipolesis mediates membrane transfer from intracytoplasmic neutrophils to platelets. eLife; 8;e44031.

















Leave a Reply