Rudd, K. E. et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet 395 (10219), 200–211 (2020).
Iannuzzi, J. P. et al. Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and Meta-Analysis. Gastroenterology 162 (1), 122–134 (2022).
Singer, M. et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama 315 (8), 801–810 (2016).
Sternby, H. et al. Determinants of Severity in Acute Pancreatitis: A Nation-wide Multicenter Prospective Cohort Study. Ann. Surg. 270 (2), 348–355 (2019).
Beyer, G. et al. S3-Leitlinie Pankreatitis (Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten e.V. (DGVS), 2021).
Lankisch, P. G., Apte, M. & Banks, P. A. Acute Pancreat. Lancet, 386(9988): 85–96. (2015).
Cecconi, M. et al. Sepsis and septic shock. Lancet 392 (10141), 75–87 (2018).
Ohkura, N., Kitagawa, Y. & Sakaguchi, S. Development and maintenance of regulatory T cells. Immunity 38 (3), 414–423 (2013).
Vignali, D. A., Collison, L. W. & Workman, C. J. How regulatory T cells work. Nat. Rev. Immunol. 8 (7), 523–532 (2008).
Huehn, J., Beyer, M. & Corthay, A. Epigenetic and transcriptional control of Foxp3 + regulatory T cells. How do regulatory T cells work? Semin Immunol. 27 (1), 10–18 (2015).
Griffith, J. W., Sokol, C. L. & Luster, A. D. Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu. Rev. Immunol. 32, 659–702 (2014).
Iellem, A. et al. Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells. J. Exp. Med. 194 (6), 847–853 (2001).
Gombert, M. et al. CCL1-CCR8 interactions: an axis mediating the recruitment of T cells and Langerhans-type dendritic cells to sites of atopic skin inflammation. J. Immunol. 174 (8), 5082–5091 (2005).
Yoshie, O. & Matsushima, K. CCR4 and its ligands: from bench to bedside. Int. Immunol. 27 (1), 11–20 (2015).
Piseddu, I. et al. Constitutive Expression of CCL22 Is Mediated by T Cell-Derived GM-CSF. J. Immunol. 205 (8), 2056–2065 (2020).
Wiedemann, G. M. et al. Cancer cell-derived IL-1α induces CCL22 and the recruitment of regulatory T cells. Oncoimmunology 5 (9), e1175794 (2016).
Anz, D. et al. Suppression of intratumoral CCL22 by type i interferon inhibits migration of regulatory T cells and blocks cancer progression. Cancer Res. 75 (21), 4483–4493 (2015).
Bischoff, L. et al. Cellular mechanisms of CCL22-mediated attenuation of autoimmune diabetes. J. Immunol. 194 (7), 3054–3064 (2015).
Dogan, R. N. et al. CCL22 regulates experimental autoimmune encephalomyelitis by controlling inflammatory macrophage accumulation and effector function. J. Leukoc. Biol. 89 (1), 93–104 (2011).
Kim, H. O. et al. Expression of CCL1 and CCL18 in atopic dermatitis and psoriasis. Clin. Exp. Dermatol. 37 (5), 521–526 (2012).
Warford, J. et al. Human Brain Chemokine and Cytokine Expression in Sepsis: A Report of Three Cases. Can. J. Neurol. Sci. 44 (1), 96–104 (2017).
Asai, A. et al. CCL1 released from M2b macrophages is essentially required for the maintenance of their properties. J. Leukoc. Biol. 92 (4), 859–867 (2012).
Zen, Y. et al. Possible involvement of CCL1-CCR8 interaction in lymphocytic recruitment in IgG4-related sclerosing cholangitis. J. Hepatol. 59 (5), 1059–1064 (2013).
Rapp, M. et al. CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes. J. Exp. Med. 216 (5), 1170–1181 (2019).
Jia, W. et al. Regulatory T cells are protective in systemic inflammation response syndrome induced by zymosan in mice. PLoS One. 8 (5), e64397 (2013).
Tatura, R. et al. Relevance of Foxp3(+) regulatory T cells for early and late phases of murine sepsis. Immunology 146 (1), 144–156 (2015).
Chen, K. et al. Prognostic value of CD4(+)CD25(+) Tregs as a valuable biomarker for patients with sepsis in ICU. World J. Emerg. Med. 6 (1), 40–43 (2015).
Huang, H. et al. High circulating CD39(+) regulatory T cells predict poor survival for sepsis patients. Deregulation of T cell response in sepsis. Int. J. Infect. Dis. 30, 57–63 (2015).
Ono, S. et al. Removal of increased circulating CD4 + CD25+Foxp3 + regulatory T cells in patients with septic shock using hemoperfusion with polymyxin B-immobilized fibers. Surgery 153 (2), 262–271 (2013).
Stier, M. T. et al. Metabolic adaptations rewire CD4(+) T cells in a subset-specific manner in human critical illness with and without sepsis. Nat. Immunol. 27 (2), 236–249 (2026).
Milivojcevic Bevc, I. et al. Redefining Immune Dynamics in Acute Pancreatitis: The Protective Role of Galectin-3 Deletion and Treg Cell Enhancement. Biomolecules, 14(6). (2024).
Zhang, H. et al. The m6A regulatory gene YTHDF3 alleviates acute pancreatitis by modulating CD45RA+ resting treg cells: A novel immunomodulatory biomarker. Med. (Baltim). 104 (37), e44443 (2025).
Glaubitz, J. et al. Experimental pancreatitis is characterized by rapid T cell activation, Th2 differentiation that parallels disease severity, and improvement after CD4(+) T cell depletion. Pancreatology 20 (8), 1637–1647 (2020).
Faix, J. D. Biomarkers of sepsis. Crit. Rev. Clin. Lab. Sci. 50 (1), 23–36 (2013).
Pierrakos, C. et al. Biomarkers of sepsis: time for a reappraisal. Crit. Care. 24 (1), 287 (2020).
Piseddu, I. et al. Innate Immune Activation Is a Strong Suppressor of CCL22 and Impedes Regulatory T Cell-Dendritic Cell Interaction (Immunology, 2025).
Bergersen, K. V. et al. Early cytokine signatures and clinical phenotypes discriminate persistent from resolving MRSA bacteremia. BMC Infect. Dis. 25 (1), 231 (2025).
Seleznik, G. M. et al. Lymphotoxin β receptor signaling promotes development of autoimmune pancreatitis. Gastroenterology 143 (5), 1361–1374 (2012).
Komatsu, M. et al. The utility of serum C-C chemokine ligand 1 in sarcoidosis: A comparison to IgG4-related disease. Cytokine 133, 155123 (2020).
Hao, S. et al. A novel polypeptide molecule attenuates atopic dermatitis by targeting CCR8-CCL1 axis. Int. Immunopharmacol. 170, 116051 (2026).
Sha, J. et al. Interaction between nasal epithelial cells and Tregs in allergic rhinitis responses to allergen via CCL1/CCR8. Front. Immunol. 16, 1526081 (2025).
Nalisa, M. et al. Chemokine receptor 8 expression may be linked to disease severity and elevated interleukin 6 secretion in acute pancreatitis. World J. Gastrointest. Pathophysiol. 12 (6), 115–133 (2021).
Chen, G. Y. & Nuñez, G. Sterile inflammation: sensing and reacting to damage. Nat. Rev. Immunol. 10 (12), 826–837 (2010).
Wiersinga, W. J. & van der Poll, T. Immunopathophysiology Hum. sepsis EBioMedicine, 86: 104363. (2022).
Xie, B. et al. Gut-derived memory γδ T17 cells exacerbate sepsis-induced acute lung injury in mice. Nat. Commun. 15 (1), 6737 (2024).
McCutcheon, C. R. et al. Group B Streptococcal Membrane Vesicles Induce Proinflammatory Cytokine Production and Are Sensed in an NLRP3 Inflammasome-Dependent Mechanism in a Human Macrophage-like Cell Line. ACS Infect. Dis. 11 (2), 453–462 (2025).
Schuetz, P., Albrich, W. & Mueller, B. Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future. BMC Med. 9, 107 (2011).
Miura, F. et al. Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis. J. Hepatobiliary Pancreat. Sci. 25 (1), 31–40 (2018).
Glaubitz, J. et al. Activated regulatory T-cells promote duodenal bacterial translocation into necrotic areas in severe acute pancreatitis. Gut 72 (7), 1355–1369 (2023).
Wang, W. et al. CD4 + CD25 + CD127 high cells as a negative predictor of multiple organ failure in acute pancreatitis. World J. Emerg. Surg. 12, 7 (2017).
Minkov, G. A., Yovtchev, Y. P. & Halacheva, K. S. Increased Circulating CD4 + CD25+CD127low/neg Regulatory T-cells as a Prognostic Biomarker in Acute Pancreatitis. Pancreas 46 (8), 1003–1010 (2017).
Bandyopadhyay, S., Samajdar, S. S. & Das, S. Ulinastatin for the treatment of severe acute pancreatitis: a systematic review and meta-analysis. BMC Gastroenterol. 25 (1), 629 (2025).
Pan, Y. et al. Ulinastatin ameliorates tissue damage of severe acute pancreatitis through modulating regulatory T cells. J. Inflamm. (Lond). 14, 7 (2017).