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Nevertheless, the specific contribution of Atg7 in CD4\u207a T cells sensitive immune responses in inflammatory bowel disease (IBD) remains largely unclear. This study explores the functional significance and regulatory mechanisms of CD4\u207a T cell\u2010specific Atg7 in IBD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Real\u2010Time Quantitative Reverse Transcription PCR (qRT\u2010PCR), western blotting analysis, flow cytometry and immunohistochemistry were employed to evaluate ATG7 expression in peripheral blood and colonic mucosal biopsies from IBD patients. Peripheral CD4\u207a T cells were transfected with lentivirus vectors encoding either <jats:italic>ATG7<\/jats:italic> (LV\u2010<jats:italic>ATG7<\/jats:italic>) or <jats:italic>ATG7<\/jats:italic> short hairpin RNA (LV\u2010sh<jats:italic>ATG7<\/jats:italic>). Furthermore, mice with a CD4\u207a T cell conditional knockout of <jats:italic>Atg7<\/jats:italic> (<jats:italic>Atg7<jats:sup>\u0394CD4<\/jats:sup><\/jats:italic>) were generated, and CD4<jats:sup>+<\/jats:sup> T cells of splenic origin were subjected to RNA\u2010seq.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>ATG7<\/jats:italic> level was markedly elevated in inflamed mucosa tissues and peripheral blood CD4<jats:sup>+<\/jats:sup> T cells of patients with active Crohn's disease compared to healthy individuals. Overexpression of <jats:italic>ATG7<\/jats:italic> suppressed Th1 differentiation while enhancing the induction of iTreg cells. <jats:italic>Atg7<jats:sup>\u0394CD4<\/jats:sup><\/jats:italic> mice exhibited exacerbated result of 2,4,6\u2010trinitrobenzenesulphonic acid\u2010induced experimental colitis, as did <jats:italic>Rag1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice adoptively transferred with CD45<jats:sup>RBhigh<\/jats:sup> CD4<jats:sup>+<\/jats:sup> T cells from <jats:italic>Atg7<jats:sup>\u0394CD4<\/jats:sup><\/jats:italic> donors. RNA\u2010seq analysis revealed that E26 transformation\u2010specific sequence\u20101 (<jats:italic>Ets1<\/jats:italic>) acts downstream of <jats:italic>Atg7<\/jats:italic> and mediates its regulatory effects on Th1 and Treg cell differentiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data indicate that Atg7 alleviates mucosal inflammation by modulating Th1\/Treg differentiation through the regulation of Ets1 expression. Thus, CD4\u207a T cell\u2010expressed Atg7 may serve as a promising therapeutic approach for IBD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Atg7 expression was significantly elevated in the inflamed mucosa and blood CD4<jats:sup>+<\/jats:sup> T cells of patients with active Crohn's disease.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Specific\u2010knockout of Atg7 in CD4<jats:sup>+<\/jats:sup> T cells leads to exacerbated colitis severity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Ets1 functions as a target of Atg7, where it inhibits Th1 cell differentiation and promotes Treg cell differentiation.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70462","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T05:56:22Z","timestamp":1756706182000},"source":"Crossref","is-referenced-by-count":4,"title":["Atg7 in CD4<sup>+<\/sup> T cells improves intestinal mucosal inflammation by regulating Ets1\u2010mediated T cell differentiation"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1870-3276","authenticated-orcid":false,"given":"Yue\u2010Tao","family":"Zhou","sequence":"first","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases Wuxi School of Medicine Jiangnan University  Wuxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan\u2010Gui","family":"Zhang","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases Wuxi School of Medicine Jiangnan University  Wuxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u2010Yuan","family":"Du","sequence":"additional","affiliation":[{"name":"Wuxi School of Medicine Jiangnan University  Wuxi People's 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