Interferon regulatory factor 5 involves the pathogenesis of emphysema through NLRP3 and Ly6C expressing cells

Interferon regulatory factor 5 involves the pathogenesis of emphysema through NLRP3 and Ly6C expressing cells

  • Vogelmeier, C. F. et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am. J. Respir. Crit. Care Med. 195, 557–582 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Puchelle, E., Zahm, J. M., Tournier, J. M. & Coraux, C. Airway epithelial repair, regeneration, and remodeling after injury in chronic obstructive pulmonary disease. Proc. Am. Thorac. Soc. 3, 726–733 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Perotin, J. M. et al. Delay of airway epithelial wound repair in COPD is associated with airflow obstruction severity. Respir. Res. 15, 151 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Heijink, I. H., Brandenburg, S. M., Postma, D. S. & van Oosterhout, A. J. Cigarette smoke impairs airway epithelial barrier function and cell-cell contact recovery. Eur. Respir. J. 39, 419–428 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Aufderheide, M., Scheffler, S., Ito, S., Ishikawa, S. & Emura, M. Ciliatoxicity in human primary bronchiolar epithelial cells after repeated exposure at the air-liquid interface with native mainstream smoke of K3R4F cigarettes with and without charcoal filter. Exp. Toxicol. Pathol. 67, 407–411 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xue, H. & Li, M. X. MicroRNA-150 protects against cigarette smoke-induced lung inflammation and airway epithelial cell apoptosis through repressing p53: microRNA-150 in CS-induced lung inflammation. Hum. Exp. Toxicol. 37, 920–928 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pan, X. et al. Interleukin-35 expression protects against cigarette smoke-induced lung inflammation in mice. Biomed. Pharmacother. 110, 727–732 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Vij, N., Chandramani-Shivalingappa, P., Van Westphal, C., Hole, R. & Bodas, M. Cigarette smoke-induced autophagy impairment accelerates lung aging, COPD-emphysema exacerbations and pathogenesis. Am. J. Physiol. Cell Physiol. 314, C73–C87 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Rutgers, S. R. et al. Ongoing airway inflammation in patients with COPD who do not currently smoke. Thorax 55, 12–18 (2000).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tashkin, D. P. et al. Bronchodilator responsiveness in patients with COPD. Eur. Respir. J. 31, 742–750 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Guay, C. A. et al. Trends in COPD severe exacerbations, and all-cause and respiratory mortality, before and after implementation of newer long-acting bronchodilators in a large population-based cohort. BMC Pulm. Med. 24, 450 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tamura, T., Yanai, H., Savitsky, D. & Taniguchi, T. The IRF family transcription factors in immunity and oncogenesis. Annu. Rev. Immunol. 26, 535–584 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Krausgruber, T. et al. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat. Immunol. 12, 231–238 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Takaoka, A. et al. Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 434, 243–249 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Weiss, M., Blazek, K., Byrne, A. J., Perocheau, D. P. & Udalova, I. A. IRF5 is a specific marker of inflammatory macrophages in vivo. Mediators Inflamm. 2013, 245804 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Barnes, P. J. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J. Allergy Clin. Immunol. 138, 16–27 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ban, T., Sato, G. R. & Tamura, T. Regulation and role of the transcription factor IRF5 in innate immune responses and systemic lupus erythematosus. Int. Immunol. 30, 529–536 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Song, S. et al. Inhibition of IRF5 hyperactivation protects from lupus onset and severity. J. Clin. Invest. 130, 6700–6717 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Draijer, C. et al. Human asthma is characterized by more IRF5+ M1 and CD206+ M2 macrophages and less IL-10+ M2-like macrophages around airways compared with healthy airways. J. Allergy Clin. Immunol. 140, 280–283 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Turan, N. et al. Neutrophilic asthma is associated with smoking, high numbers of IRF5+, and low numbers of IL10+ macrophages. Front. Allergy 2, 676930 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jang, Y. O. et al. Fecal microbial transplantation and a high fiber diet attenuates emphysema development by suppressing inflammation and apoptosis. Exp. Mol. Med. 52, 1128–1139 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Heo, S.-H., Park, S. Y., Kim, N. H., Song, E. & Lee, S. W. Interferon regulatory factor 5 involves immune responses through regulation of ly6c expression. J. Immunol. 210, 243.207 (2023).

    Article 

    Google Scholar
     

  • Sung, Y. H. et al. Highly efficient gene knockout in mice and zebrafish with RNA-guided endonucleases. Genome Res. 24, 125–131 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, Y. et al. Generation of knockout mice by Cpf1-mediated gene targeting. Nat. Biotechnol. 34, 808–810 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chung, C. et al. Fine particulate matter aggravates smoking induced lung injury via NLRP3/caspase-1 pathway in COPD. J. Inflamm. 21, 13 (2024).

    Article 
    CAS 

    Google Scholar
     

  • Knudsen, L., Weibel, E. R., Gundersen, H. J., Weinstein, F. V. & Ochs, M. Assessment of air space size characteristics by intercept (chord) measurement: an accurate and efficient stereological approach. J. Appl. Physiol. 108, 412–421 (2010).

    Article 
    PubMed 

    Google Scholar
     

  • Koressaar, T. et al. Primer3_masker: integrating masking of template sequence with primer design software. Bioinformatics 34, 1937–1938 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wright, S. S. et al. A bacterial toxin co-opts caspase-3 to disable active gasdermin D and limit macrophage pyroptosis. Cell Rep. 43, 114004 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, W. et al. Allergen protease-activated stress granule assembly and gasdermin D fragmentation control interleukin-33 secretion. Nat. Immunol. 23, 1021–1030 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Taabazuing, C. Y., Okondo, M. C. & Bachovchin, D. A. Pyroptosis and apoptosis pathways engage in bidirectional crosstalk in monocytes and macrophages. Cell Chem. Biol. 24, 507–514 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cutolo, M., Campitiello, R., Gotelli, E. & Soldano, S. The role of M1/M2 macrophage polarization in rheumatoid arthritis synovitis. Front. Immunol. 13, 867260 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ochando, J. C. & Chen, S. H. Myeloid-derived suppressor cells in transplantation and cancer. Immunol. Res. 54, 275–285 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, Z., Gu, Y., Shin, A., Zhang, S. & Ginhoux, F. Analysis of myeloid cells in mouse tissues with flow cytometry. STAR Protoc. 1, 100029 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhou, J., Nefedova, Y., Lei, A. & Gabrilovich, D. Neutrophils and PMN-MDSC: their biological role and interaction with stromal cells. Semin. Immunol. 35, 19–28 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Youn, J. I., Collazo, M., Shalova, I. N., Biswas, S. K. & Gabrilovich, D. I. Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice. J. Leukoc. Biol. 91, 167–181 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Veglia, F., Sanseviero, E. & Gabrilovich, D. I. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat. Rev. Immunol. 21, 485–498 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Crocker, P. R., McMillan, S. J. & Richards, H. E. CD33-related siglecs as potential modulators of inflammatory responses. Ann. N. Y. Acad. Sci. 1253, 102–111 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hedl, M., Yan, J., Witt, H. & Abraham, C. IRF5 Is required for bacterial clearance in human M1-polarized macrophages, and IRF5 immune-mediated disease risk variants modulate this outcome. J. Immunol. 202, 920–930 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Belchamber, K. B. R. & Donnelly, L. E. Macrophage dysfunction in respiratory disease. Results Probl. Cell Differ. 62, 299–313 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Clements, M. et al. Differential Ly6C expression after renal ischemia–reperfusion identifies unique macrophage populations. J. Am. Soc. Nephrol. 27, 159–170 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tarique, A. A. et al. Phenotypic, functional, and plasticity features of classical and alternatively activated human macrophages. Am. J. Respir. Cell Mol. Biol. 53, 676–688 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Frank, D. & Vince, J. E. Pyroptosis versus necroptosis: similarities, differences, and crosstalk. Cell Death Differ. 26, 99–114 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Plataki, M. et al. Apoptotic mechanisms in the pathogenesis of COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 1, 161–171 (2006).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu, Y. et al. The role of the NLRP3 inflammasome in chronic inflammation in asthma and chronic obstructive pulmonary disease. Immun. Inflamm. Dis. 10, e750 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Feng, Y. et al. Pyroptosis in inflammation-related respiratory disease. J. Physiol. Biochem. 78, 721–737 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bain, C. C. et al. Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat. Immunol. 15, 929–937 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gibbings, S. L. et al. Three unique interstitial macrophages in the murine lung at steady state. Am. J. Respir. Cell Mol. Biol. 57, 66–76 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Plantinga, M. et al. Conventional and monocyte-derived CD11b+ dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen. Immunity 38, 322–335 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Li, Y. H. et al. Occurrences and functions of Ly6Chi and Ly6Clo macrophages in health and disease. Front. Immunol. 13, 901672 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Saiwai, H. et al. Ly6C+ Ly6G myeloid-derived suppressor cells play a critical role in the resolution of acute inflammation and the subsequent tissue repair process after spinal cord injury. J. Neurochem. 125, 74–88 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Goldmann, O., Nwofor, O. V., Chen, Q. & Medina, E. Mechanisms underlying immunosuppression by regulatory cells. Front. Immunol. 15, 1328193 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hegde, S., Leader, A. M. & Merad, M. MDSC: Markers, development, states, and unaddressed complexity. Immunity 54, 875–884 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Guthridge, M. A. et al. Growth factor pleiotropy is controlled by a receptor Tyr/Ser motif that acts as a binary switch. EMBO J. 25, 479–489 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hercus, T. R. et al. The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease. Blood 114, 1289–1298 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • van de Laar, L., Coffer, P. J. & Woltman, A. M. Regulation of dendritic cell development by GM-CSF: molecular control and implications for immune homeostasis and therapy. Blood 119, 3383–3393 (2012).

    Article 
    PubMed 

    Google Scholar
     

  • Becher, B., Tugues, S. & Greter, M. GM-CSF: from growth factor to central mediator of tissue inflammation. Immunity 45, 963–973 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhao, W. et al. Enrichment of Ly6Chi monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model. Hum. Vaccin. Immunother. 13, 2872–2882 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Awad, M., Sen’kova, A., Zenkova, M. & Markov, O. The impact of cytokines and tumour-conditioned medium on the properties of murine in vitro generated myeloid-derived suppressor cells. Scand. J. Immunol. 101, e70001 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wu, C. et al. Tumor microenvironment following gemcitabine treatment favors differentiation of immunosuppressive Ly6Chigh myeloid cells. J. Immunol. 204, 212–223 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Helft, J. et al. GM-CSF mouse bone marrow cultures comprise a heterogeneous population of CD11c+MHCII+ macrophages and dendritic cells. Immunity 42, 1197–1211 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar