{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T12:41:29Z","timestamp":1793882489116,"version":"4.7.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Interleukin-6 (IL-6) is a key mediator cytokine of the immune response as well as a regulator of many physiological and pathological processes. In Crohn\u2019s disease (CD), cytokine imbalance rules the intestinal microenvironment and leads to chronic inflammation of the gut. Pro-inflammatory cytokines are generally upregulated in inflammatory bowel disease (IBD) including TNF\u03b1 and IL-6. Consequently, drugs that target these cytokines have been long sought and approved. Despite the short-term success in treating CD patients with anti-TNF\u03b1, many patients stopped responding to treatment, which made IL-6 an alternative target to alleviate inflammation in these patients. IL-6 has long been approached as part of the therapeutic strategies to treat CD and other inflammatory disorders. Clinical trials of CD patients have targeted IL-6 signaling in different mechanisms: blocking IL-6, neutralizing IL-6 receptor (IL-6R), or trapping the soluble IL-6\/IL-6R complex. These trials have faced challenges and side effects in patients with gastrointestinal perforations and ulcers, for example, all of which highlight the dual role of IL-6 during intestinal inflammation and the need for this cytokine for intestinal tissue integrity. IL-6 is involved in a complex of upstream regulators and downstream signaling cascades and maintaining a physiological level of IL-6 in the blood and in the intestine is key for achieving health and homeostasis. In this review, we describe IL-6 biology and signaling and its involvement in intestinal health and inflammation. We also discuss the current strategies for targeting IL-6 pathways in CD patients, as well as molecular regulators representing potential therapeutic targets for IL-6 attenuation.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1295230","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T14:09:23Z","timestamp":1701439763000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":105,"title":["The dual role of interleukin-6 in Crohn\u2019s disease pathophysiology"],"prefix":"10.3389","volume":"14","author":[{"given":"Ala\u2019","family":"Alhendi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh A.","family":"Naser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020831","article-title":"Inflammatory bowel disease","volume":"347","author":"Podolsky","year":"2002","journal-title":"New Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31711-1","article-title":"Crohn\u2019s disease","volume":"389","author":"Torres","year":"2017","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17058-X","article-title":"Culture of Mycobacterium avium subspecies paratuberculosis from the blood of patients with Crohn\u2019s disease","volume":"364","author":"Naser","year":"2004","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60026-9","article-title":"Crohn\u2019s disease","volume":"380","author":"Baumgart","year":"2012","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2013.12.003","article-title":"Master regulator of intestinal disease: IL-6 in chronic inflammation and cancer development","volume":"26","author":"Waldner","year":"2014","journal-title":"Semin Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00384-018-3069-8","article-title":"Evaluation of interleukin-6 and its soluble receptor components sIL-6R and sgp130 as markers of inflammation in inflammatory bowel diseases","volume":"33","author":"Nikolaus","year":"2018","journal-title":"Int J colorectal Dis"},{"key":"B7","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s13099-020-00387-0","article-title":"MiR-146a rs2910164 G\u2009>\u2009C polymorphism modulates Notch-1\/IL-6 signaling during infection: a possible risk factor for Crohn\u2019s disease","volume":"12","author":"Keewan","year":"2020","journal-title":"Gut Pathog"},{"key":"B8","doi-asserted-by":"publisher","first-page":"204","DOI":"10.7150\/ijbs.51362","article-title":"Biological characteristics of IL-6 and related intestinal diseases","volume":"17","author":"Guo","year":"2021","journal-title":"Int J Biol Sci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(90)90149-L","article-title":"Significant increase of interleukin 6 production in blood mononuclear leukocytes obtained from patients with active imflammatory bowel disease","volume":"47","author":"Suzuki","year":"1990","journal-title":"Life Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1993.tb05997.x","article-title":"Enhanced secretion of tumor necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn\u2019s disease","volume":"94","author":"Reinacker","year":"1993","journal-title":"Clin Exp Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1042\/CS20110340","article-title":"IL-6\/IL-6 receptor system and its role in physiological and pathological conditions","volume":"122","author":"Mihara","year":"2012","journal-title":"Clin Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20148","article-title":"Il-6 signaling in inflammatory bowel disease: pathophysiological role and clinical relevance","volume":"13","author":"Mudter","year":"2007","journal-title":"Inflammatory bowel Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/75068","article-title":"Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in crohn disease and experimental colitis in vivo","volume":"6","author":"Atreya","year":"2000","journal-title":"Nat Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/324073a0","article-title":"Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin","volume":"324","author":"Hirano","year":"1986","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","first-page":"115327","DOI":"10.1016\/j.bmc.2020.115327","article-title":"A panoramic review of IL-6: Structure, pathophysiological roles and inhibitors","volume":"28","author":"Kaur","year":"2020","journal-title":"Bioorganic medicinal Chem"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(21)00103-X","article-title":"Interleukin-6: obstacles to targeting a complex cytokine in critical illness","volume":"9","author":"McElvaney","year":"2021","journal-title":"Lancet Respir Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1097\/CM9.0000000000002792","article-title":"Insights into the molecular mechanisms and therapeutic implications of interleukin-6 for inflammatory bowel disease","author":"Tie","year":"2023","journal-title":"Chin Med J"},{"key":"B18","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1096\/fj.99-1003rev","article-title":"The soluble interleukin 6 receptor: mechanisms of production and implications in disease","volume":"15","author":"Jones","year":"2001","journal-title":"FASEB J"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-0419-z","article-title":"Translating IL-6 biology into effective treatments","volume":"16","author":"Choy","year":"2020","journal-title":"Nat Rev Rheumatol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3153","article-title":"IL-6 as a keystone cytokine in health and disease","volume":"16","author":"Hunter","year":"2015","journal-title":"Nat Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.coi.2015.02.008","article-title":"The IL-6\/gp130\/STAT3 signaling axis: recent advances towards specific inhibition","volume":"34","author":"Garbers","year":"2015","journal-title":"Curr Opin Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-07-102137","article-title":"Transgenic blockade of interleukin 6 transsignaling abrogates inflammation","volume":"111","author":"Rabe","year":"2008","journal-title":"Blood J Am Soc Hematol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s12964-018-0268-4","article-title":"Activation of the JAK\/STAT3 and PI3K\/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells","volume":"16","author":"Zegeye","year":"2018","journal-title":"Cell Communication Signaling"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2017.55","article-title":"Bacteroidales recruit IL-6-producing intraepithelial lymphocytes in the colon to promote barrier integrity","volume":"11","author":"Kuhn","year":"2018","journal-title":"Mucosal Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0114195","article-title":"IL-6 stimulates intestinal epithelial proliferation and repair after injury","volume":"9","author":"Kuhn","year":"2014","journal-title":"PloS One"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600960","article-title":"IL-6 signaling regulates small intestinal crypt homeostasis","volume":"199","author":"Jeffery","year":"2017","journal-title":"J Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.4161\/21688370.2014.977176","article-title":"Claudin-2 as a mediator of leaky gut barrier during intestinal inflammation","volume":"3","author":"Luettig","year":"2015","journal-title":"Tissue Barriers"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.238147","article-title":"Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium","volume":"286","author":"Suzuki","year":"2011","journal-title":"J Biol Chem"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085345","article-title":"Interleukin-6 modulation of intestinal epithelial tight junction permeability is mediated by JNK pathway activation of claudin-2 gene","volume":"9","author":"Al-Sadi","year":"2014","journal-title":"PloS One"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700316","article-title":"Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells","volume":"85","author":"Prasad","year":"2005","journal-title":"Lab Invest"},{"key":"B31","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1136\/gut.2006.094375","article-title":"Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn\u2019s disease","volume":"56","author":"Zeissig","year":"2007","journal-title":"Gut"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13941","article-title":"Histone H3K9 methylation regulates chronic stress and IL-6\u2013induced colon epithelial permeability and visceral pain","volume":"32","author":"Wiley","year":"2020","journal-title":"Neurogastroenterol Motil"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.281.3.R1013","article-title":"Intestinal permeability is reduced and IL-10 levels are increased in septic IL-6 knockout mice","volume":"281","author":"Wang","year":"2001","journal-title":"Am J Physiology-Regulatory Integr Comp Physiol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.6.3194","article-title":"IL-6 induces NF-\u03baB activation in the intestinal epithelia","volume":"171","author":"Wang","year":"2003","journal-title":"J Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4942","article-title":"ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-\u03b1-activated vascular endothelium under flow","volume":"106","author":"Yang","year":"2005","journal-title":"Blood"},{"key":"B36","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1159\/000506364","article-title":"Treatment algorithms for Crohn\u2019s disease","volume":"101","author":"Sulz","year":"2020","journal-title":"Digestion"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.01.012","article-title":"A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn\u2019s disease","volume":"126","author":"Ito","year":"2004","journal-title":"Gastroenterology"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-314562","article-title":"Randomised trial and open-label extension study of an anti-interleukin-6 antibody in Crohn\u2019s disease (ANDANTE I and II)","volume":"68","author":"Danese","year":"2019","journal-title":"Gut"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2014.07.006","article-title":"Tocilizumab in rheumatoid arthritis: a case study of safety evaluations of a large postmarketing data set from multiple data sources","volume":"44","author":"Curtis","year":"2015","journal-title":"Semin Arthritis Rheum"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-011-1827-x","article-title":"Lower gastrointestinal perforation in rheumatoid arthritis patients treated with conventional DMARDs or tocilizumab: a systematic literature review","volume":"30","author":"Gout","year":"2011","journal-title":"Clin Rheumatol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.02.062","article-title":"Therapeutic interleukin-6 trans-signaling inhibition by olamkicept (sgp130Fc) in patients with active inflammatory bowel disease","volume":"160","author":"Schreiber","year":"2021","journal-title":"Gastroenterology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1096\/fj.02-1211fje","article-title":"TGF-\u03b2 down-regulates IL-6 signaling in intestinal epithelial cells: Critical role of SMAD-2","volume":"17","author":"Walia","year":"2003","journal-title":"FASEB J"},{"key":"B43","doi-asserted-by":"publisher","first-page":"3928","DOI":"10.7150\/thno.70762","article-title":"5-HT2B-mediated serotonin activation in enterocytes suppresses colitis-associated cancer initiation and promotes cancer progression","volume":"12","author":"Mao","year":"2022","journal-title":"Theranostics"},{"key":"B44","doi-asserted-by":"publisher","first-page":"e12673","DOI":"10.1111\/cpr.12673","article-title":"Inhibition of CREB-mediated ZO-1 and activation of NF-\u03baB-induced IL-6 by colonic epithelial MCT4 destroys intestinal barrier function","volume":"52","author":"Zhang","year":"2019","journal-title":"Cell proliferation"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.009093","article-title":"Monocarboxylate transporter 4 (MCT4) is a high affinity transporter capable of exporting lactate in high-lactate microenvironments","volume":"294","author":"Contreras-Baeza","year":"2019","journal-title":"J Biol Chem"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01342","article-title":"Discovery of clinical candidate AZD0095, a selective inhibitor of monocarboxylate transporter 4 (MCT4) for oncology","volume":"66","author":"Goldberg","year":"2022","journal-title":"J Medicinal Chem"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.19","article-title":"The matricellular protein CCN1 promotes mucosal healing in murine colitis through IL-6","volume":"8","author":"Choi","year":"2015","journal-title":"Mucosal Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902792","article-title":"Matricellular protein CCN1 activates a proinflammatory genetic program in murine macrophages","volume":"184","author":"Bai","year":"2010","journal-title":"J Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.12.4457","article-title":"Identification of integrin \u03b1M\u03b22 as an adhesion receptor on peripheral blood monocytes for Cyr61 (CCN1) and connective tissue growth factor (CCN2): immediate-early gene products expressed in atherosclerotic lesions","volume":"99","author":"Schober","year":"2002","journal-title":"Blood J Am Soc Hematol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"503","DOI":"10.3390\/biom11040503","article-title":"Syndecan-4 as a pathogenesis factor and therapeutic target in cancer","volume":"11","author":"Onyeisi","year":"2021","journal-title":"Biomolecules"},{"key":"B51","doi-asserted-by":"publisher","first-page":"944","DOI":"10.3390\/molecules26040944","article-title":"Strategies to target ADAM17 in disease: from its discovery to the iRhom revolution","volume":"26","author":"Calligaris","year":"2021","journal-title":"Molecules"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu","article-title":"Attenuation of excess TNF-a release in crohn\u2019s disease by silencing of iRHOMs 1\/2 and the restoration of TGF-b mediated immunosuppression through modulation of TACE trafficking","volume":"13","author":"Louis","year":"2022","journal-title":"Front Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1086\/510385","article-title":"The role of microbes in crohn\u2019s disease","volume":"44","author":"Eckburg","year":"2007","journal-title":"Clin Infect Dis"},{"key":"B54","first-page":"RA27","article-title":"Integrating theories of the etiology of Crohn\u2019s Disease On the etiology of Crohn\u2019s Disease: Questioning the Hypotheses","volume":"12","author":"Chamberlin","year":"2006","journal-title":"Med Sci Monitor"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i36.4558","article-title":"High prevalence of viable Mycobacterium avium subspecies paratuberculosis in Crohn\u2019s disease","volume":"16","author":"Mendoza","year":"2010","journal-title":"World J Gastroenterol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1297-9716-45-54","article-title":"From mouth to macrophage: mechanisms of innate immune subversion by Mycobacterium avium subsp. paratuberculosis","volume":"45","author":"Arsenault","year":"2014","journal-title":"Veterinary Res"},{"key":"B57","article-title":"Ein eigenthuemlicher fall von tuberculose beim rind","volume":"21","author":"Johne","year":"1895","journal-title":"Dtsch Z. Tiermed. Pathol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1136\/flgastro-2020-101471","article-title":"Anti-Mycobacterium paratuberculosis (MAP) therapy for Crohn\u2019s disease: An overview and update","volume":"12","author":"Honap","year":"2021","journal-title":"Frontline Gastroenterol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.045526","article-title":"High prevalence of Mycobacterium avium subspecies paratuberculosis IS900 DNA in gut tissues from individuals with Crohn\u2019s disease","volume":"54","author":"Autschbach","year":"2005","journal-title":"Gut"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.41.7.2915-2923.2003","article-title":"Detection and verification of Mycobacterium avium subsp. paratuberculosis in fresh ileocolonic mucosal biopsy specimens from individuals with and without Crohn\u2019s disease","volume":"41","author":"Bull","year":"2003","journal-title":"J Clin Microbiol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.3390\/microorganisms11061520","article-title":"Viable Mycobacterium avium subsp. paratuberculosis Colonizes Peripheral Blood of Inflammatory Bowel Disease Patients","volume":"11","author":"Estevinho","year":"2023","journal-title":"Microorganisms"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.3390\/microorganisms8071006","article-title":"Notch-1 signaling modulates macrophage polarization and immune defense against Mycobacterium avium paratuberculosis infection in inflammatory diseases","volume":"8","author":"Keewan","year":"2020","journal-title":"Microorganisms"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgast-2018-000216","article-title":"TNF\u03b1 inhibitors exacerbate Mycobacterium paratuberculosis infection in tissue culture: A rationale for poor response of patients with Crohn\u2019s disease to current approved therapy","volume":"5","author":"Qasem","year":"2018","journal-title":"BMJ Open Gastroenterol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s13099-016-0127-z","article-title":"A single capsule formulation of RHB-104 demonstrates higher anti-microbial growth potency for effective treatment of Crohn\u2019s disease associated with Mycobacterium avium subspecies paratuberculosis","volume":"8","author":"Qasem","year":"2016","journal-title":"Gut Pathog"},{"key":"B65","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s13099-016-0115-3","article-title":"RHB-104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn\u2019s disease associated with Mycobacterium paratuberculosis","volume":"8","author":"Alcedo","year":"2016","journal-title":"Gut Pathog"},{"key":"B66","doi-asserted-by":"publisher","first-page":"513","DOI":"10.3390\/biomedicines8110513","article-title":"Anti-MAP triple therapy supports immunomodulatory therapeutic response in Crohn\u2019s disease through downregulation of NF-\u03baB activation in the absence of MAP detection","volume":"8","author":"Qasem","year":"2020","journal-title":"Biomedicines"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.14309\/01.ajg.0000592108.53051.68","article-title":"643\u2003RHB-104, a fixed-dose, oral antibiotic combination against mycobacterium avium paratuberculosis (MAP) infection, is effective in moderately to severely active crohn\u2019s disease","volume":"114","author":"Graham","year":"2019","journal-title":"Off J Am Coll Gastroenterol | ACG"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1295230\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T14:09:27Z","timestamp":1701439767000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1295230\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,1]]},"references-count":67,"alternative-id":["10.3389\/fimmu.2023.1295230"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1295230","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,1]]},"article-number":"1295230"}}