{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:52:57Z","timestamp":1792720377632,"version":"4.5.0"},"reference-count":60,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,3,10]]},"abstract":"<jats:p>A proper balance between Th17 and T regulatory cells (Treg cells) is critical for generating protective immune responses while minimizing autoimmunity. We show that the Tec family kinase Itk (IL2-inducible T cell kinase), a component of T cell receptor (TCR) signaling pathways, influences this balance by regulating cross talk between TCR and cytokine signaling. Under both Th17 and Treg cell differentiation conditions, Itk\u2212\/\u2212 CD4+ T cells develop higher percentages of functional FoxP3+ cells, associated with increased sensitivity to IL-2. Itk\u2212\/\u2212 CD4+ T cells also preferentially develop into Treg cells in vivo. We find that Itk-deficient T cells exhibit reduced TCR-induced phosphorylation of mammalian target of rapamycin (mTOR) targets, accompanied by downstream metabolic alterations. Surprisingly, Itk\u2212\/\u2212 cells also exhibit reduced IL-2\u2013induced mTOR activation, despite increased STAT5 phosphorylation. We demonstrate that in wild-type CD4+ T cells, TCR stimulation leads to a dose-dependent repression of Pten. However, at low TCR stimulation or in the absence of Itk, Pten is not effectively repressed, thereby uncoupling STAT5 phosphorylation and phosphoinositide-3-kinase (PI3K) pathways. Moreover, Itk-deficient CD4+ T cells show impaired TCR-mediated induction of Myc and miR-19b, known repressors of Pten. Our results demonstrate that Itk helps orchestrate positive feedback loops integrating multiple T cell signaling pathways, suggesting Itk as a potential target for altering the balance between Th17 and Treg cells.<\/jats:p>","DOI":"10.1084\/jem.20131459","type":"journal-article","created":{"date-parts":[[2014,2,17]],"date-time":"2014-02-17T23:02:21Z","timestamp":1392678141000},"page":"529-543","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":179,"title":["Itk-mediated integration of T cell receptor and cytokine signaling regulates the balance between Th17 and regulatory T cells"],"prefix":"10.1084","volume":"211","author":[{"given":"Julio","family":"Gomez-Rodriguez","sequence":"first","affiliation":[{"name":"National Human Genome Research Institute 1 , 2 , 3 , and 4"},{"name":"National Institute of Allergy and Infectious Diseases 1 , 2 , 3 , and 4"},{"name":"National Institute of Arthritis and Musculoskeletal and Skin 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