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Src homology 2\u2010containing protein tyrosine phosphatase 2 (SHP2) is a non\u2010receptor protein tyrosine phosphatase that acts as a key regulator of immune cell\u2010mediated inflammation. Although studies have described the role of SHP2 in autoimmune diseases, its influence on the development of regulatory T cells (Tregs) was undefined, which plays a critical role in immune homeostasis. Here, we found that imiquimod (IMQ)\u2010induced psoriasis symptoms were milder in <jats:italic>Lck<\/jats:italic>\u2010Cre;SHP2<jats:sup>f\/f<\/jats:sup> mice than those in SHP2<jats:sup>f\/f<\/jats:sup> mice, including reduced inflammatory cell infiltration and keratinocyte proliferation. The reduced Th17\/Treg ratio in psoriasis models in <jats:italic>Lck<\/jats:italic>\u2010Cre;SHP2<jats:sup>f\/f<\/jats:sup> mice suggests that SHP2 regulates the balance of Th17\/Treg. In vitro, the deficiency of SHP2 promotes the differentiation of T cells into Tregs. In the model of adoptive transfer colitis, the SHP2\u2010deficient CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>\u2212<\/jats:sup>CD45RB<jats:sup>high<\/jats:sup> T cells differentiated into a greater number of Tregs within the recipient mice, resulting in attenuated symptoms of colitis. Moreover, cotransfer experiments confirmed that the deficiency of SHP2 does not affect the immunosuppressive function of Tregs. These findings establish that SHP2 reduces Treg differentiation and further confirm that SHP2 inhibitors could be utilized in the treatment of autoimmune diseases.<\/jats:p>","DOI":"10.1002\/mco2.70310","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T09:36:51Z","timestamp":1754041011000},"source":"Crossref","is-referenced-by-count":2,"title":["T Cell\u2010Specific Deficiency of Src Homology 2\u2010Containing Protein Tyrosine Phosphatase 2 Ameliorates Psoriasis and Colitis by Promoting Treg Differentiation"],"prefix":"10.1002","volume":"6","author":[{"given":"Shuqiong","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology Chemistry and Biomedicine Innovation Center (ChemBIC) School of Life Sciences Nanjing University  Nanjing China"},{"name":"Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University  Xuzhou 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