{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T21:17:13Z","timestamp":1793999833392,"version":"4.8.0"},"reference-count":142,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2024206398"],"award-info":[{"award-number":["H2024206398"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Interleukin-37 (IL-37) is a potent anti-inflammatory cytokine that plays a crucial protective role in cancer, autoimmune diseases, and inflammatory diseases though its unique dual intracellular and extracellular action pathways. This review highlights the significance of IL-37 in common respiratory diseases. Specifically, IL-37 can alleviate asthma by inhibiting Th2\/Th17 immune responses, inhibiting the release of epithelial-derived alarmins (TSLP and IL-33), and attenuating airway remodeling. In pulmonary infections, IL-37 modulates host responses by mitigating virus-induced hyperinflammation and inhibiting viral replication, as observed in COVID-19 and influenza, while also regulating immunopathology in Mycobacterium tuberculosis and fungal infections. Moreover, in non-small cell lung cancer (NSCLC), IL-37 directly suppresses tumor proliferation and migration, and restrains tumor progression through immunomodulation and angiogenesis regulation. In pulmonary fibrosis, IL-37 reduces collagen deposition and promotes autophagy, thereby counteracting interstitial fibrosis. Collectively, these findings demonstrate that IL-37 serves as a crucial immunomodulator in respiratory diseases, and targeting IL-37 offers novel insights and strategic opportunities for clinical intervention. This review systematically summarizes the molecular mechanisms of IL-37 and discusses its clinical therapeutic potential.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1675791","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T05:17:59Z","timestamp":1762751879000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Interleukin-37 in respiratory diseases: molecular mechanisms and immune modulation"],"prefix":"10.3389","volume":"16","author":[{"given":"Jing","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaona","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30157-0","article-title":"Chronic respiratory diseases: A global view","volume":"8","author":"Labaki","year":"2020","journal-title":"Lancet Respir Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30105-3","article-title":"Prevalence and attributable health burden of chronic respiratory diseases, 1990-2017: A systematic analysis for the global burden of disease study 2017","volume":"8","author":"Soriano","year":"2020","journal-title":"Lancet Respir Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-022-00964-2","article-title":"Tissue-resident immunity in the lung: A first-line defense at the environmental interface","volume":"44","author":"Zazara","year":"2022","journal-title":"Semin Immunopathology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"34s","DOI":"10.1183\/09031936.01.00252501","article-title":"Pharmacological treatment of asthma today","volume":"34","author":"Rabe","year":"2001","journal-title":"Eur Respir J Suppl"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7003","article-title":"The effects of nigella sativa on respiratory, allergic and immunologic disorders, evidence from experimental and clinical studies, a comprehensive and updated review","volume":"35","author":"Saadat","year":"2021","journal-title":"Phytother Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1944","article-title":"Il-37 is a fundamental inhibitor of innate immunity","volume":"11","author":"Nold","year":"2010","journal-title":"Nat Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1619011114","article-title":"Interleukin 37 reverses the metabolic cost of inflammation, increases oxidative respiration, and improves exercise tolerance","volume":"114","author":"Cavalli","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B8","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/nri2691","article-title":"The Il-1 family: regulators of immunity","volume":"10","author":"Sims","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.11.010","article-title":"The interleukin-1 family: back to the future","volume":"39","author":"Garlanda","year":"2013","journal-title":"Immunity"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132612","article-title":"Immunological and inflammatory functions of the interleukin-1 family","volume":"27","author":"Dinarello","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2406","article-title":"From Il-2 to Il-37: the expanding spectrum of anti-inflammatory cytokines","volume":"13","author":"Banchereau","year":"2012","journal-title":"Nat Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.012","article-title":"Interleukin-1 and related cytokines in the regulation of inflammation and immunity","volume":"50","author":"Mantovani","year":"2019","journal-title":"Immunity"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109705","article-title":"The role of Il-37 in skin and connective tissue diseases","volume":"122","author":"Pan","year":"2020","journal-title":"BioMed Pharmacother"},{"key":"B14","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1189\/jlb.5RU0816-341R","article-title":"A protective role of Il-37 in cancer: A new hope for cancer patients","volume":"101","author":"Abulkhir","year":"2017","journal-title":"J Leukoc Biol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2015.08.006","article-title":"Insights into Il-37, the role in autoimmune diseases","volume":"14","author":"Xu","year":"2015","journal-title":"Autoimmun Rev"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-016-0137-7","article-title":"The role of Il-37 in non-cancerous diseases","volume":"23","author":"Ding","year":"2017","journal-title":"Pathol Oncol Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.22034\/iji.2018.39386","article-title":"Role of interleukin-37 in inflammatory and autoimmune diseases","volume":"15","author":"Wang","year":"2018","journal-title":"Iran J Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12605","article-title":"Suppression of inflammation and acquired immunity by Il-37","volume":"281","author":"Cavalli","year":"2018","journal-title":"Immunol Rev"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.2.1169","article-title":"Four new members expand the interleukin-1 superfamily","volume":"275","author":"Smith","year":"2000","journal-title":"J Biol Chem"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6184","article-title":"Identification and gene organization of three novel members of the Il-1 family on human chromosome 2","volume":"66","author":"Busfield","year":"2000","journal-title":"Genomics"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.14.10308","article-title":"Identification and initial characterization of four novel members of the interleukin-1 family","volume":"275","author":"Kumar","year":"2000","journal-title":"J Biol Chem"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1006\/cyto.2000.0799","article-title":"Il-1h, an interleukin 1-related protein that binds Il-18 receptor\/Il-1rrp","volume":"13","author":"Pan","year":"2001","journal-title":"Cytokine"},{"key":"B23","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.cyto.2014.03.002","article-title":"Long-range DNA interactions at the Il-1\/Il-36\/Il-37 gene cluster (2q13) are induced by activation of monocytes","volume":"68","author":"Sharaf","year":"2014","journal-title":"Cytokine"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1177\/039463201202500105","article-title":"Il-37 (Il-1f7) the newest anti-inflammatory cytokine which suppresses immune responses and inflammation","volume":"25","author":"Tete","year":"2012","journal-title":"Int J Immunopathol Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1586\/1744666x.2014.971014","article-title":"Immunobiology of Il-37: mechanism of action and clinical perspectives","volume":"10","author":"Quirk","year":"2014","journal-title":"Expert Rev Clin Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1819672116","article-title":"Interleukin-37 monomer is the active form for reducing innate immunity","volume":"116","author":"Eisenmesser","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201545828","article-title":"Suppression of innate inflammation and immunity by interleukin-37","volume":"46","author":"Dinarello","year":"2016","journal-title":"Eur J Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1684\/ecn.2011.0288","article-title":"Il-37: A new anti-inflammatory cytokine of the Il-1 family","volume":"22","author":"Boraschi","year":"2011","journal-title":"Eur Cytokine Netw"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00167","article-title":"New insights in the immunobiology of Il-1 family members","volume":"4","author":"van de Veerdonk","year":"2013","journal-title":"Front Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2002.6752","article-title":"Genomic organization of the interleukin-1 locus","volume":"79","author":"Taylor","year":"2002","journal-title":"Genomics"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2014.11.025","article-title":"Il-37: A new player in immune tolerance","volume":"72","author":"Chen","year":"2015","journal-title":"Cytokine"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/srep14478","article-title":"Expression of Il-37 contributes to the immunosuppressive property of human Cd4+Cd25+ Regulatory T cells","volume":"5","author":"Shuai","year":"2015","journal-title":"Sci Rep"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1042\/bj20040217","article-title":"Interleukin-1 homologues Il-1f7b and Il-18 contain functional Mrna instability elements within the coding region responsive to lipopolysaccharide","volume":"381","author":"Bufler","year":"2004","journal-title":"Biochem J"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111982108","article-title":"Interleukin 37 expression protects mice from colitis","volume":"108","author":"McNamee","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.696605","article-title":"Current understanding of Il-37 in human health and disease","volume":"12","author":"Su","year":"2021","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.3390\/ijms19041149","article-title":"The role, involvement and function(S) of interleukin-35 and interleukin-37 in disease pathogenesis","volume":"19","author":"Bello","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-019-0277-8","article-title":"The Il-1 family of cytokines and receptors in rheumatic diseases","volume":"15","author":"Dinarello","year":"2019","journal-title":"Nat Rev Rheumatol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12967-015-0394-3","article-title":"Interleukin-37 is increased in ankylosing spondylitis patients and associated with disease activity","volume":"13","author":"Chen","year":"2015","journal-title":"J Transl Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109343","article-title":"Interleukin-37 alleviates myocardial injury induced by coxsackievirus B3 via inhibiting neutrophil extracellular traps formation","volume":"113","author":"Li","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110098","article-title":"Interleukin-37 ameliorates atherosclerosis by regulating autophagy-mediated endothelial cell apoptosis and inflammation","volume":"118","author":"Xiao","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.3390\/brainsci12060723","article-title":"Recent advances in progresses and prospects of Il-37 in central nervous system diseases","volume":"12","author":"Li","year":"2022","journal-title":"Brain Sci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.2147\/cia.S230186","article-title":"Plasma interleukin-37 is elevated in acute ischemic stroke patients and probably associated with 3-month functional prognosis","volume":"15","author":"Zhang","year":"2020","journal-title":"Clin Interv Aging"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1055\/a-2153-8836","article-title":"Research progress on the role and mechanism of Il-37 in liver diseases","volume":"43","author":"Jiang","year":"2023","journal-title":"Semin Liver Dis"},{"key":"B44","doi-asserted-by":"publisher","first-page":"54","DOI":"10.32607\/20758251-2019-11-4-54-64","article-title":"The role of interleukin-37 in the pathogenesis of allergic diseases","volume":"11","author":"Shilovskiy","year":"2019","journal-title":"Acta Naturae"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/all.15072","article-title":"Il-37 regulates allergic inflammation by counterbalancing pro-inflammatory Il-1 and Il-33","volume":"77","author":"Schr\u00f6der","year":"2022","journal-title":"Allergy"},{"key":"B46","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.cytogfr.2019.10.003","article-title":"Insight into interleukin-37: the potential therapeutic target in allergic diseases","volume":"49","author":"Huang","year":"2019","journal-title":"Cytokine Growth Factor Rev"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.788741","article-title":"Interleukin-37: A link between Covid-19, diabetes, and the black fungus","volume":"12","author":"Tokajian","year":"2021","journal-title":"Front Microbiol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2021.01.019","article-title":"Interleukin-37 as a biomarker of mortality risk in patients with sepsis","volume":"82","author":"Wu","year":"2021","journal-title":"J Infect"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2021.155760","article-title":"Dual role of Il-37 in the progression of tumors","volume":"150","author":"Zhu","year":"2022","journal-title":"Cytokine"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2012.10.017","article-title":"Analysis of nuclear localization of interleukin-1 family cytokines by flow cytometry","volume":"387","author":"Ross","year":"2013","journal-title":"J Immunol Methods"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.8.5477","article-title":"The Il-1 family member 7b translocates to the nucleus and down-regulates proinflammatory cytokines","volume":"180","author":"Sharma","year":"2008","journal-title":"J Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1324140111","article-title":"Role of caspase-1 in nuclear translocation of Il-37, release of the cytokine, and Il-37 inhibition of innate immune responses","volume":"111","author":"Bulau","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B53","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1006\/cyto.2002.0873","article-title":"Interleukin-1f7b (Il-1h4\/Il-1f7) is processed by caspase-1 and mature Il-1f7b binds to the Il-18 receptor but does not induce Ifn-gamma production","volume":"18","author":"Kumar","year":"2002","journal-title":"Cytokine"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106476","article-title":"Il-37 is protective in allergic contact dermatitis through mast cell inhibition","volume":"83","author":"Li","year":"2020","journal-title":"Int Immunopharmacol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1821111116","article-title":"Role for nuclear interleukin-37 in the suppression of innate immunity","volume":"116","author":"Li","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.444","article-title":"Intracellular Il-37b interacts with smad3 to suppress multiple signaling pathways and the metastatic phenotype of tumor cells","volume":"36","author":"Luo","year":"2017","journal-title":"Oncogene"},{"key":"B57","doi-asserted-by":"publisher","first-page":"495","DOI":"10.3892\/etm.2022.11422","article-title":"Biology of interleukin-37 and its role in autoimmune diseases (Review)","volume":"24","author":"Zeng","year":"2022","journal-title":"Exp Ther Med"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1424626112","article-title":"Extracellular forms of Il-37 inhibit innate inflammation in vitro and in vivo but require the Il-1 family decoy receptor Il-1r8","volume":"112","author":"Li","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/ni968","article-title":"Sigirr, a negative regulator of toll-like receptor-interleukin 1 receptor signaling","volume":"4","author":"Wald","year":"2003","journal-title":"Nat Immunol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"22396","DOI":"10.1038\/s41598-025-05623-8","article-title":"High-dose Il-37 promotes inflammatory activity of macrophage via preferential ligation of the Il-18r\u03b1","volume":"15","author":"Zhang","year":"2025","journal-title":"Sci Rep"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30253","article-title":"Il-37-induced activation of glycogen synthase kinase 3\u03b2 Promotes Il-1r8\/Sigirr phosphorylation, internalization, and degradation in lung epithelial cells","volume":"236","author":"Li","year":"2021","journal-title":"J Cell Physiol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/s1074-7613(00)80013-8","article-title":"Interleukin-18 binding protein: A novel modulator of the Th1 cytokine response","volume":"10","author":"Novick","year":"1999","journal-title":"Immunity"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.212519099","article-title":"A complex of the Il-1 homologue Il-1f7b and Il-18-binding protein reduces Il-18 activity","volume":"99","author":"Bufler","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12616","article-title":"Interleukin-18: biological properties and role in disease pathogenesis","volume":"281","author":"Kaplanski","year":"2018","journal-title":"Immunol Rev"},{"key":"B65","doi-asserted-by":"publisher","first-page":"83","DOI":"10.2119\/molmed.2017.00022","article-title":"Il-37 suppresses myd88-mediated inflammatory responses in human aortic valve interstitial cells","volume":"23","author":"Zhan","year":"2017","journal-title":"Mol Med"},{"key":"B66","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1016\/j.jaci.2006.02.023","article-title":"Toll-like receptor function and signaling","volume":"117","author":"Kaisho","year":"2006","journal-title":"J Allergy Clin Immunol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1101\/gr.4338005","article-title":"A genome-wide survey of structural variation between human and chimpanzee","volume":"15","author":"Newman","year":"2005","journal-title":"Genome Res"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1564357","article-title":"The distinct roles of Il-37 and Il-38 in non-small cell lung carcinoma and their clinical implications","volume":"16","author":"Zhang","year":"2025","journal-title":"Front Immunol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2024.110368","article-title":"Insights into the multifaceted role of interleukin-37 on human immune cell regulation","volume":"268","author":"Teufel","year":"2024","journal-title":"Clin Immunol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa192","article-title":"Il-37 inhibits M1-like macrophage activation to ameliorate temporomandibular joint inflammation through the Nlrp3 pathway","volume":"59","author":"Luo","year":"2020","journal-title":"Rheumatol (Oxford)"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00056","article-title":"Interleukin 37 suppresses M1 macrophage polarization through inhibition of the notch1 and nuclear factor kappa B pathways","volume":"8","author":"Zhou","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2019.05.009","article-title":"Il-37 inhibits the maturation of dendritic cells through the Il-1r8-Tlr4-Nf-Kb pathway","volume":"1864","author":"Liu","year":"2019","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106391","article-title":"A new target for the treatment of inflammatory bowel disease: interleukin-37","volume":"83","author":"Jia","year":"2020","journal-title":"Int Immunopharmacol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"3884","DOI":"10.3390\/ijms19123884","article-title":"Anti-inflammatory effect of Il-37-producing T-cell population in Dss-induced chronic inflammatory bowel disease in mice","volume":"19","author":"Chen","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.603649","article-title":"Modulation of liver inflammation and fibrosis by interleukin-37","volume":"12","author":"Mountford","year":"2021","journal-title":"Front Immunol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2023.115816","article-title":"Interleukin-37 relieves Pm2.5-triggered lung injury by inhibiting autophagy through the Akt\/Mtor signaling pathway in vivo and in vitro","volume":"269","author":"Cao","year":"2024","journal-title":"Ecotoxicology Environ Saf"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2017.04.010","article-title":"Il-37 induces autophagy in hepatocellular carcinoma cells by inhibiting the Pi3k\/Akt\/Mtor pathway","volume":"87","author":"Li","year":"2017","journal-title":"Mol Immunol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.12659\/msm.922979","article-title":"Interleukin 37 (Il-37) reduces high glucose-induced inflammation, oxidative stress, and apoptosis of podocytes by inhibiting the Stat3-cyclophilin a (Cypa) signaling pathway","volume":"26","author":"Zhang","year":"2020","journal-title":"Med Sci Monit"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.115.306543","article-title":"Il-37 is a novel proangiogenic factor of developmental and pathological angiogenesis","volume":"35","author":"Yang","year":"2015","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"6113","DOI":"10.1038\/s41598-017-06124-z","article-title":"Interleukin 37 promotes angiogenesis through Tgf-B Signaling","volume":"7","author":"Zhao","year":"2017","journal-title":"Sci Rep"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.3ma0220-207rr","article-title":"The indirect antiangiogenic effect of Il-37 in the tumor microenvironment","volume":"107","author":"Mei","year":"2020","journal-title":"J Leukoc Biol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-016-0293-3","article-title":"Interleukin-37 suppresses tumor growth through inhibition of angiogenesis in non-small cell lung cancer","volume":"35","author":"Ge","year":"2016","journal-title":"J Exp Clin Cancer Res"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2023.104759","article-title":"Attenuated airways inflammation and remodeling in Il-37a and Il-37b transgenic mice with an ovalbumin-induced chronic asthma","author":"Cui","year":"2023","journal-title":"Cell Immunol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113684","article-title":"Interleukin-37 ameliorates cigarette smoke-induced lung inflammation in mice","volume":"155","author":"Wu","year":"2022","journal-title":"BioMed Pharmacother"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02482","article-title":"Interleukin-37 ameliorates influenza pneumonia by attenuating macrophage cytokine production in a Mapk-dependent manner","volume":"10","author":"Qi","year":"2019","journal-title":"Front Microbiol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-018-0820-9","article-title":"Interleukin-37 attenuates bleomycin-induced pulmonary inflammation and fibrosis in mice","volume":"41","author":"Li","year":"2018","journal-title":"Inflammation"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1801515","article-title":"Il-37 attenuates lung fibrosis by inducing autophagy and regulating Tgf-B1 production in mice","volume":"203","author":"Kim","year":"2019","journal-title":"J Immunol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(22)02125-0","article-title":"Asthma","volume":"401","author":"Porsbjerg","year":"2023","journal-title":"Lancet"},{"key":"B89","doi-asserted-by":"publisher","first-page":"e20221094","DOI":"10.1084\/jem.20221094","article-title":"T helper 2 cells in asthma","volume":"220","author":"Harker","year":"2023","journal-title":"J Exp Med"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2678","article-title":"Asthma phenotypes: the evolution from clinical to molecular approaches","volume":"18","author":"Wenzel","year":"2012","journal-title":"Nat Med"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-110119-091711","article-title":"Group 2 innate lymphoid cells: team players in regulating asthma","volume":"39","author":"Rodriguez-Rodriguez","year":"2021","journal-title":"Annu Rev Immunol"},{"key":"B92","doi-asserted-by":"publisher","first-page":"eaat1604","DOI":"10.1126\/sciimmunol.aat1604","article-title":"Type 2 immunity: expanding our view","volume":"3","author":"Lloyd","year":"2018","journal-title":"Sci Immunol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2020.10.002","article-title":"Mechanisms of non-type 2 asthma","volume":"66","author":"Hudey","year":"2020","journal-title":"Curr Opin Immunol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1111\/all.12566","article-title":"Il-37 requires Il-18r\u03b1 and Sigirr\/Il-1r8 to Diminish allergic airway inflammation in mice","volume":"70","author":"Lunding","year":"2015","journal-title":"Allergy"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203515","article-title":"Cytokine antibody array-based analysis of Il-37 treatment effects in asthma","volume":"13","author":"Gao","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2015.09.009","article-title":"Anti-inflammatory activity of Il-37 in asthmatic children: correlation with inflammatory cytokines Tnf-A, Il-B, Il-6 and Il-17a","volume":"221","author":"Charrad","year":"2016","journal-title":"Immunobiology"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrtlng.2020.04.017","article-title":"Evaluation serum levels of Ykl-40, periostin, and some inflammatory cytokines together with Il-37, a new anti-inflammatory cytokine, in patients with stable and exacerbated asthma","volume":"50","author":"Yildiz","year":"2021","journal-title":"Heart Lung"},{"key":"B98","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1186\/s12931-017-0675-x","article-title":"The potential of interleukin-37 as an effective therapeutic agent in asthma","volume":"18","author":"Zhang","year":"2017","journal-title":"Respir Res"},{"key":"B99","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.intimp.2017.12.010","article-title":"Interleukin-37 alleviates airway inflammation and remodeling in asthma via inhibiting the activation of Nf-Kb and Stat3 signalings","volume":"55","author":"Huang","year":"2018","journal-title":"Int Immunopharmacol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12223","article-title":"Il-37 alleviates house dust mite-induced chronic allergic asthma by targeting Tslp through the Nf-Kb and Erk1\/2 signaling pathways","volume":"97","author":"Meng","year":"2019","journal-title":"Immunol Cell Biol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01445","article-title":"Anti-allergic inflammatory activity of interleukin-37 is mediated by novel signaling cascades in human eosinophils","volume":"9","author":"Zhu","year":"2018","journal-title":"Front Immunol"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1111\/all.13395","article-title":"Il-37 inhibits Il-4\/Il-13-induced Ccl11 production and lung eosinophilia in murine allergic asthma","volume":"73","author":"Lv","year":"2018","journal-title":"Allergy"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2022.14.5.505","article-title":"Il-24 contributes to neutrophilic asthma in an Il-17a-dependent manner and is suppressed by Il-37","volume":"14","author":"Feng","year":"2022","journal-title":"Allergy Asthma Immunol Res"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.018","article-title":"The cytokines of asthma","volume":"50","author":"Lambrecht","year":"2019","journal-title":"Immunity"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-018-8720-1","article-title":"Mast cell-mediated orchestration of the immune responses in human allergic asthma: current insights","volume":"56","author":"Elieh Ali Komi","year":"2019","journal-title":"Clin Rev Allergy Immunol"},{"key":"B106","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.imlet.2016.08.004","article-title":"Increased expression of thymic stromal lymphopoietin in induced sputum from asthmatic children","volume":"178","author":"Berra\u00efes","year":"2016","journal-title":"Immunol Lett"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112525","article-title":"Il-37 protects against house dust mite-induced airway inflammation and airway epithelial barrier dysfunction via inhibiting store-operated calcium entry","volume":"138","author":"Wang","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2021.112890","article-title":"Interleukin-37 inhibits inflammation activation and disease severity of Pm2.5-induced airway hyperresponsiveness","volume":"227","author":"Wang","year":"2021","journal-title":"Ecotoxicol Environ Saf"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-022-01596-w","article-title":"The role of Il-1 family of cytokines and receptors in pathogenesis of Covid-19","volume":"71","author":"Makaremi","year":"2022","journal-title":"Inflammation Res"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa713","article-title":"Correlation between early plasma interleukin 37 responses with low inflammatory cytokine levels and benign clinical outcomes in severe acute respiratory syndrome coronavirus 2 infection","volume":"223","author":"Li","year":"2021","journal-title":"J Infect Dis"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70229","article-title":"Il-37 mitigates the inflammatory response in macrophages induced by Sars-Cov-2 omicron infection through the Nf-Kb signaling pathway","volume":"6","author":"Qi","year":"2025","journal-title":"MedComm (2020)"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2021.155702","article-title":"Interleukin-37 is down-regulated in serum of patients with severe coronavirus disease 2019 (Covid-19)","volume":"148","author":"Ahmed","year":"2021","journal-title":"Cytokine"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.mgene.2021.100989","article-title":"Interleukin-37 gene polymorphism and susceptibility to Coronavirus disease 19 among Iraqi patients","volume":"31","author":"Ahmed","year":"2022","journal-title":"Meta Gene"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12435","article-title":"Il-37 possesses both anti-inflammatory and antiviral effects against middle east respiratory syndrome Coronavirus infection","volume":"8","author":"Qi","year":"2025","journal-title":"Anim Model Exp Med"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2016.31.11.1717","article-title":"Clinical progression and cytokine profiles of middle east respiratory syndrome coronavirus infection","volume":"31","author":"Kim","year":"2016","journal-title":"J Korean Med Sci"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00320","article-title":"Host immune response to influenza a virus infection","volume":"9","author":"Chen","year":"2018","journal-title":"Front Immunol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.22638","article-title":"Influenza a virus inhibits influenza virus replication by inducing Il-37","volume":"33","author":"Zhou","year":"2019","journal-title":"J Clin Lab Anal"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2023-077431","article-title":"Prevent Tb to end Tb","volume":"382","author":"Basnyat","year":"2023","journal-title":"BMJ"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12326","article-title":"Il-37 expression is upregulated in patients with tuberculosis and induces macrophages towards an M2-like phenotype","volume":"82","author":"Huang","year":"2015","journal-title":"Scand J Immunol"},{"key":"B120","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.molimm.2016.09.018","article-title":"Tuberculosis-sensitized monocytes sustain immune response of interleukin-37","volume":"79","author":"Zhang","year":"2016","journal-title":"Mol Immunol"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0225556","article-title":"Il-18\/Il-37\/Ip-10 signalling complex as a potential biomarker for discriminating active and latent Tb","volume":"14","author":"Wawrocki","year":"2019","journal-title":"PLoS One"},{"key":"B122","article-title":"The diagnostic value of combined detection of microrna-155, Tnf-A and Il-37 for active pulmonary tuberculosis in the elderly","volume":"14","author":"Yu","year":"2022","journal-title":"Am J Transl Res"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169922","article-title":"Il-37 confers protection against mycobacterial infection involving suppressing inflammation and modulating T cell activation","volume":"12","author":"Liu","year":"2017","journal-title":"PLoS One"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1111\/1348-0421.12444","article-title":"Association of Il-37 gene polymorphisms with susceptibility to tuberculosis in saudi subjects","volume":"60","author":"Allam","year":"2016","journal-title":"Microbiol Immunol"},{"key":"B125","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.ijtb.2021.08.003","article-title":"Interleukin-37 gene polymorphism and susceptibility to pulmonary tuberculosis among Iraqi patients","volume":"69","author":"Ali","year":"2022","journal-title":"Indian J Tuberc"},{"key":"B126","doi-asserted-by":"publisher","first-page":"6758","DOI":"10.1038\/s41598-018-24509-6","article-title":"Transcriptional landscape of mycobacterium tuberculosis infection in macrophages","volume":"8","author":"Roy","year":"2018","journal-title":"Sci Rep"},{"key":"B127","article-title":"Mannose-capped lipoarabinomannan from mycobacterium tuberculosis induces Il-37 production via upregulating Erk1\/2 and P38 in human type ii alveolar epithelial cells","volume":"8","author":"Huang","year":"2015","journal-title":"Int J Clin Exp Med"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2022.127221","article-title":"Epidemiological characteristics and antibiotic resistance mechanisms of streptococcus pneumoniae: an updated review","volume":"266","author":"Li","year":"2023","journal-title":"Microbiol Res"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1159\/000469661","article-title":"Il-37 causes excessive inflammation and tissue damage in murine pneumococcal pneumonia","volume":"9","author":"Schauer","year":"2017","journal-title":"J Innate Immun"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2023.101728","article-title":"Immunity to fungi in the lung","volume":"66","author":"Heung","year":"2023","journal-title":"Semin Immunol"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004462","article-title":"Il-37 inhibits inflammasome activation and disease severity in murine aspergillosis","volume":"10","author":"Moretti","year":"2014","journal-title":"PLoS Pathog"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2014.00762","article-title":"Protective host defense against disseminated candidiasis is impaired in mice expressing human interleukin-37","volume":"5","author":"van de Veerdonk","year":"2014","journal-title":"Front Microbiol"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007098","article-title":"The role of interleukin-1 cytokine family (Il-1\u03b2, il-37) and interleukin-12 cytokine family (Il-12, Il-35) in eumycetoma infection pathogenesis","volume":"13","author":"Abushouk","year":"2019","journal-title":"PloS Negl Trop Dis"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01740-y","article-title":"Lung cancer immunotherapy: progress, pitfalls, and promises","volume":"22","author":"Lahiri","year":"2023","journal-title":"Mol Cancer"},{"key":"B135","doi-asserted-by":"publisher","first-page":"5346","DOI":"10.3390\/ijms23105346","article-title":"Cellular and molecular profiling of tumor microenvironment and early-stage lung cancer","volume":"23","author":"Pirlog","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1002\/cnr2.1151","article-title":"Il-37: an anti-inflammatory cytokine with antitumor functions","volume":"2","author":"Mei","year":"2019","journal-title":"Cancer Rep (Hoboken)"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.12628","article-title":"Il-37 inhibits invasion and metastasis in non-small cell lung cancer by suppressing the Il-6\/Stat3 signaling pathway","volume":"9","author":"Jiang","year":"2018","journal-title":"Thorac Cancer"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.3233\/cbm-170732","article-title":"Effects of exogenous Il-37 on the biological characteristics of human lung adenocarcinoma A549 cells and the chemotaxis of regulatory T cells","volume":"21","author":"Chen","year":"2018","journal-title":"Cancer biomark"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.3892\/or.2016.4995","article-title":"Ccl22 and Il-37 inhibit the proliferation and epithelial-mesenchymal transition process of Nsclc A549 cells","volume":"36","author":"Chen","year":"2016","journal-title":"Oncol Rep"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1016\/j.crimmu.2021.08.002","article-title":"Tumor-infiltrating T-regulatory cells adapt to altered metabolism to promote tumor-immune escape","volume":"2","author":"Sarkar","year":"2021","journal-title":"Curr Res Immunol"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.405","article-title":"Intracellular mature Il-37 suppresses tumor metastasis via inhibiting Rac1 activation","volume":"37","author":"Li","year":"2018","journal-title":"Oncogene"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.526866","article-title":"Il-37 confers anti-tumor activity by regulation of M6a methylation","volume":"10","author":"Mu","year":"2020","journal-title":"Front Oncol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1675791\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T05:18:01Z","timestamp":1762751881000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1675791\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,10]]},"references-count":142,"alternative-id":["10.3389\/fimmu.2025.1675791"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1675791","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,10]]},"article-number":"1675791"}}