{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:59:10Z","timestamp":1792141150174,"version":"4.4.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"vor","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08 DK104021"],"award-info":[{"award-number":["K08 DK104021"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI166835"],"award-info":[{"award-number":["R01 AI166835"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000937","name":"Murdock Charitable Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000937","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Dysregulated differentiation of na\u00efve CD4+ T cells into T helper 17 (Th17) cells is likely a key factor predisposing to many autoimmune diseases. Therefore, better understanding how Th17 differentiation is regulated is essential to identify novel therapeutic targets and strategies to identify individuals at high risk of developing autoimmunity. Here, we extend our prior work using chemical inhibitors to provide mechanistic insight into a novel regulator of Th17 differentiation, the kinase dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). We generated a conditional knockout mouse model to validate DYRK1A as a regulator of Th17 differentiation that acts in a dose-dependent fashion at least in part by modulating interleukin (IL)-6 signaling through multiple mechanisms. We identified a new role for DYRK1A in regulating surface expression of IL-6 receptor subunits in na\u00efve CD4+ T cells, consistent with DYRK1A\u2019s impact on Th17 differentiation. Physiologic relevance is supported by findings in people with Down syndrome, in which increased expression of DYRK1A, encoded on chromosome 21, is linked to increased IL-6 responsiveness. Our findings highlight DYRK1A as a druggable target of broad therapeutic and prognostic interest in autoimmunity and immune function.<\/jats:p>","DOI":"10.1093\/immhor\/vlae005","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T14:59:43Z","timestamp":1737644383000},"source":"Crossref","is-referenced-by-count":6,"title":["Defining a novel DYRK1A-gp130\/IL-6R-pSTAT axis that regulates Th17 differentiation"],"prefix":"10.1093","volume":"9","author":[{"given":"Matthew","family":"Malueg","sequence":"first","affiliation":[{"name":"Center for Translational Immunology, Benaroya Research Institute at Virginia Mason , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7806-785X","authenticated-orcid":false,"given":"Keagan G","family":"Moo","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Benaroya Research Institute at Virginia Mason , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1368-4678","authenticated-orcid":false,"given":"Azlann","family":"Arnett","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Benaroya Research Institute at Virginia Mason , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4300-4020","authenticated-orcid":false,"given":"Thomas H","family":"Edwards","sequence":"additional","affiliation":[{"name":"Center for Systems Immunology, Benaroya Research Institute at Virginia Mason , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L","family":"Ruskin","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Benaroya Research Institute at Virginia Mason , Seattle, WA,","place":["United 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Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4123-9926","authenticated-orcid":false,"given":"Vivian H","family":"Gersuk","sequence":"additional","affiliation":[{"name":"Center for Systems Immunology, Benaroya Research Institute at Virginia Mason , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5614-3914","authenticated-orcid":false,"given":"Rebecca","family":"Partridge","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Virginia Mason Medical Center , Issaquah, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9005-1885","authenticated-orcid":false,"given":"Jane H","family":"Buckner","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Benaroya Research Institute at Virginia Mason , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4689-5092","authenticated-orcid":false,"given":"Bernard","family":"Khor","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Benaroya Research Institute at Virginia Mason , Seattle, WA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,23]]},"reference":[{"key":"2025012316021123200_vlae005-B1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3389\/fimmu.2019.00353","article-title":"Effector functions of CD4+ T cells at the site of local autoimmune inflammation\u2014lessons from rheumatoid arthritis","volume":"10","author":"Chemin","year":"2019","journal-title":"Front 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