{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T10:50:33Z","timestamp":1779187833516,"version":"3.51.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IL-1R\u2013associated kinase (IRAK) 1 is an important component of the IL-1R and TLR signaling pathways, which influence Th cell differentiation. In this study, we show that IRAK1 promotes Th17 development by mediating IL-1\u03b2\u2013induced upregulation of IL-23R and subsequent STAT3 phosphorylation, thus enabling sustained IL-17 production. Moreover, we show that IRAK1 signaling fosters Th1 differentiation by mediating T-bet induction and counteracts regulatory T cell generation. Cotransfer experiments revealed that Irak1-deficient CD4+ T cells have a cell-intrinsic defect in generating Th1 and Th17 cells under inflammatory conditions in spleen, mesenteric lymph nodes, and colon tissue. Furthermore, IRAK1 expression in T cells was shown to be essential for T cell accumulation in the inflamed intestine and mesenteric lymph nodes. Transcriptome analysis ex vivo revealed that IRAK1 promotes T cell activation and induction of gut-homing molecules in a cell-intrinsic manner. Accordingly, Irak1-deficient T cells failed to upregulate surface expression of \u03b14\u03b27 integrin after transfer into Rag1\u2212\/\u2212 mice, and their ability to induce colitis was greatly impaired. Lack of IRAK1 in recipient mice provided additional protection from colitis. Therefore, IRAK1 plays an important role in intestinal inflammation by mediating T cell activation, differentiation, and accumulation in the gut. Thus, IRAK1 is a promising novel target for therapy of inflammatory bowel diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1501874","type":"journal-article","created":{"date-parts":[[2015,11,12]],"date-time":"2015-11-12T02:29:27Z","timestamp":1447295367000},"page":"5787-5794","source":"Crossref","is-referenced-by-count":23,"title":["IRAK1 Drives Intestinal Inflammation by Promoting the Generation of Effector Th Cells with Optimal Gut-Homing Capacity"],"prefix":"10.1093","volume":"195","author":[{"given":"Alexander F","family":"Heiseke","sequence":"first","affiliation":[{"name":"Institute for Immunology, Biomedical Center Munich, Ludwig Maximilians University , D-82152 Planegg-Martinsried ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9071-7464","authenticated-orcid":false,"given":"Benjamin H","family":"Jeuk","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Biomedical Center Munich, Ludwig Maximilians University , D-82152 Planegg-Martinsried ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anamarija","family":"Markota","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Biomedical Center Munich, Ludwig Maximilians University , D-82152 Planegg-Martinsried ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Straub","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Unit, Biomedical Center Munich, Ludwig Maximilians University , D-82152 Planegg-Martinsried ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Anton","family":"Lehr","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pathologie, Medizin Campus Bodensee, Friedrichshafen , D-88048 Friedrichshafen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6982-8506","authenticated-orcid":false,"given":"Wolfgang","family":"Reindl","sequence":"additional","affiliation":[{"name":"Klinikum Mannheim II, Medizinische Klinik , D-68167 Mannheim ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne B","family":"Krug","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Biomedical Center Munich, Ludwig Maximilians University , D-82152 Planegg-Martinsried ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,12,15]]},"reference":[{"key":"2025030704271720100_r1","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1172\/JCI30587","article-title":"The fundamental basis of inflammatory bowel disease","volume":"117","author":"Strober","year":"2007","journal-title":"J. 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