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Here, it is demonstrated that E\u2010twenty\u2010six variant transcription factor 1 (ETV1) is upregulated in IBD patients and positively correlates with disease severity. Etv1 deficiency impairs CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation, proliferation, and T helper 17 (Th17)\u00a0cell differentiation, thereby ameliorating TNBS\u2010induced colitis. Moreover, Etv1 deficiency attenuates CD45RB\n                    <jats:sup>high<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2010induced colitis, characterized by a reduction in pathogenic CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in the intestinal mucosa. Pharmacological inhibition of ETV1 ameliorates colitis in recombination activating gene 1\u2010deficient mice and suppresses human IBD T cell responses ex vivo. Mechanistically, Etv1 binds to the promoter of the gene encoding the amino acid transporter solute carrier family 7 member 5 (Slc7a5), enhancing its expression and subsequent amino acid uptake to fuel T cell pathogenicity. Restoring Slc7a5 expression rescues the proliferation, differentiation, and colitogenic function of Etv1\u2010deficient CD4\u207a T cells. Clinically, SLC7A5 is upregulated in IBD, and its blockade ameliorates T cell\u2010driven colitis in vivo. Collectively, the results establish a critical role for the ETV1\u2010Slc7a5 axis in driving pathogenic CD4\u207a T cell responses in IBD, highlighting this pathway as a novel therapeutic target.\n                  <\/jats:p>","DOI":"10.1002\/advs.202511595","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T11:34:49Z","timestamp":1764934489000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ETV1 Drives CD4\n                    <sup>+<\/sup>\n                    T Cell\u2010Mediated Intestinal Inflammation in Inflammatory Bowel Disease Through Amino Acid Transporter Slc7a5"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5437-3986","authenticated-orcid":false,"given":"Yan","family":"Shi","sequence":"first","affiliation":[{"name":"Digestive Endoscopic Center Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song","family":"Wang","sequence":"additional","affiliation":[{"name":"Digestive Endoscopic Center Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqing","family":"Yan","sequence":"additional","affiliation":[{"name":"Digestive Endoscopic Center Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dafan","family":"Chen","sequence":"additional","affiliation":[{"name":"Digestive Endoscopic Center Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caiyun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Shanghai Tenth People's Hospital Tongji University School of Medicine  Shanghai 200072 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinjian","family":"Wan","sequence":"additional","affiliation":[{"name":"Digestive Endoscopic Center Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"},{"name":"Department of Gastroenterology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2024-334010"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mucimm.2024.03.010"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-023-00871-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-024-00612-x"},{"key":"e_1_2_9_5_1","first-page":"3","volume":"19","author":"Yan Y.","year":"2025","journal-title":"J. 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