{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:57:34Z","timestamp":1793228254697,"version":"4.5.0"},"reference-count":87,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Gastroenterological Society of Australia"},{"DOI":"10.13039\/501100001232","name":"the Royal Australasian College of Physicians","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001232","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1173584"],"award-info":[{"award-number":["1173584"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["2033196"],"award-info":[{"award-number":["2033196"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Fielding Foundation"},{"name":"Ramaciotti Health Investment Grant","award":["2021HIG72"],"award-info":[{"award-number":["2021HIG72"]}]},{"DOI":"10.13039\/501100000925","name":"NHMRC Investigator EL1","doi-asserted-by":"publisher","award":["1194063"],"award-info":[{"award-number":["1194063"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Victorian Cancer Agency Fellowship","award":["MCRF21036"],"award-info":[{"award-number":["MCRF21036"]}]},{"name":"Galaxy Australia"},{"name":"NCRIS"},{"name":"The University of Melbourne and Queensland Government RICF"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>IBD pathogenesis is underpinned by an imbalance between excess inflammation caused by effector T-cells and inadequate suppression by regulatory T-cells (Tregs). Interleukin-37 (IL-37) is a potent, anti-inflammatory cytokine that signals via its receptors IL-1R5 and IL-1R8. Hence, augmenting anti-inflammatory mechanisms that drive IL-37 expression is a strategy to control IBD-associated inflammation. However, the role of IL-37 and its receptors in T-cells remains incompletely understood. Here, we investigated T-cell expression profiles of IL-37 and its receptors to understand the drivers of dysregulated T-cell responses in IBD and develop novel, more effective therapies. T-cell subsets from healthy control (HC), Crohn\u2019s disease (CD) and ulcerative colitis (UC) peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) were assessed for expression of IL-37 and its receptors by flow cytometry. CD3+IL-1R8+ T-cell transcriptomes underwent RNA sequencing. The phenotype and suppressive capacity of Tregs supplemented with IL-37 was assessed in vitro. Our results indicate that IL-37 and its receptors were differentially expressed among PBMC and LPMC T-cell subsets in IBD patients compared to HC. Transcription signatures unique to IBD were revealed, particularly histone and mitochondrial pathways. Remarkably, culturing Tregs with IL-37 preserved FOXP3 expression and suppressiveness at a level comparable to treatment with the well-established Treg stabilizing agent rapamycin. Altogether, our study identified differences in T-cells expressing IL-37 and its receptors that are indicative of T-cell dysfunction in IBD. These findings highlight a novel and promising avenue for restoring immune homeostasis in IBD by targeting and boosting the IL-37 signalling pathway.<\/jats:p>","DOI":"10.3390\/ijms27031540","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T14:55:11Z","timestamp":1770216911000},"page":"1540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Characteristics of T-Cells Expressing IL-37 and Its Receptors in Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Indiana","family":"Zorkau","sequence":"first","affiliation":[{"name":"Centre for Inflammatory Diseases, Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7102-3547","authenticated-orcid":false,"given":"Peter J.","family":"Eggenhuizen","sequence":"additional","affiliation":[{"name":"Centre for Inflammatory Diseases, Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8057-5774","authenticated-orcid":false,"given":"Marie","family":"Lee","sequence":"additional","affiliation":[{"name":"Centre for Inflammatory Diseases, Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-2092","authenticated-orcid":false,"given":"Steven X.","family":"Cho","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia"},{"name":"Department of Paediatrics, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7107-0650","authenticated-orcid":false,"given":"Kylie R.","family":"James","sequence":"additional","affiliation":[{"name":"Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia"},{"name":"School of Biomedical Sciences, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2248-9914","authenticated-orcid":false,"given":"Andrew M.","family":"Ellisdon","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4200-5611","authenticated-orcid":false,"given":"James C.","family":"Whisstock","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3328-2561","authenticated-orcid":false,"given":"Joshua D.","family":"Ooi","sequence":"additional","affiliation":[{"name":"Centre for Inflammatory Diseases, Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9682-4618","authenticated-orcid":false,"given":"Marcel F.","family":"Nold","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia"},{"name":"Department of Paediatrics, Monash University, Clayton, VIC 3168, Australia"},{"name":"Monash Children\u2019s Hospital, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7439-3834","authenticated-orcid":false,"given":"Claudia A.","family":"Nold-Petry","sequence":"additional","affiliation":[{"name":"The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia"},{"name":"Department of Paediatrics, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4984-8585","authenticated-orcid":false,"given":"Rimma","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Centre for Inflammatory Diseases, Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC 3168, Australia"},{"name":"Department of Gastroenterology, Monash Health, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel 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