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Adv."],"published-print":{"date-parts":[[2026,8,21]]},"abstract":"<jats:p>Transforming growth factor\u2013\u03b2 (TGF-\u03b2) is central to suppressing T cell function to maintain tolerance and immune homeostasis. The current TGF-\u03b2 signaling paradigm is however inadequate in explaining how TGF-\u03b2 controls T cell function. Here, we found a previously unappreciated, SKI-dependent mechanism of TGF-\u03b2 signaling to better explain how TGF-\u03b2 restricts T cell function to bolster tolerance. We found that SKI protein was up-regulated in activated T cells and down-regulated in response to TGF-\u03b2, indicating a reciprocal relationship between SKI and TGF-\u03b2 in controlling T cell function. T cell\u2013specific SKI deletion ameliorated spontaneous lethal autoimmunity due to T cell\u2013specific TGF\u03b2RII deletion and mitigated MOG\/CFA-induced experimental autoimmune encephalomyelitis. SKI was required for activation-induced T cell function and related molecular programs. Therefore, inhibition of TGF\u03b2R not only results in the loss of Smad-dependent function but, more importantly, leads to the gain of SKI-dependent activity, which is essential for T cell\u2013mediated autoimmunity. A critical mechanism underlying TGF-\u03b2\u2013mediated suppression of T cell function is overcoming SKI activity.<\/jats:p>","DOI":"10.1126\/sciadv.aeb7051","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:59:26Z","timestamp":1787162366000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["SKI is critical to counter TGF-\u03b2 signaling to promote T cell function and autoimmunity"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9289-7702","authenticated-orcid":true,"given":"Junying","family":"Wang","sequence":"first","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."},{"name":"Department of Microbiology-Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, 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