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Recently, populations of natural Th17 and Th1 cells (nTh17 and nTh1) with innate-like phenotype have been identified in the thymus that are distinct from conventional Th17 and Th1 cells. The absence of the Tec family kinase Interleukin-2 inducible T cell kinase (Itk) results in T cell immunodeficiency in mice and humans. Here we show that Itk negatively regulates the development of nTh1 cells that express IFN\u03b3 in a Tbet independent manner, and whose expansion can be enhanced by IL4. Furthermore, we show that robust induction of IL4 responses during <jats:italic>Trichinella spiralis<\/jats:italic> infection enhance the presence of nTh1 cells. We conclude T cell receptor signaling via Itk controls the development of natural Th1 cells, which are expanded by the presence of IL4.<\/jats:p>","DOI":"10.1038\/srep45935","type":"journal-article","created":{"date-parts":[[2017,4,13]],"date-time":"2017-04-13T09:09:30Z","timestamp":1492074570000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["T-Bet independent development of IFN\u03b3 secreting natural T helper 1 cell population in the absence of Itk"],"prefix":"10.1038","volume":"7","author":[{"given":"Arun K.","family":"Kannan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Mohinta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weishan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Koylass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith A.","family":"Appleton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avery","family":"August","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,4,13]]},"reference":[{"key":"BFsrep45935_CR1","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/nri3824","volume":"15","author":"MH Kaplan","year":"2015","unstructured":"Kaplan, M. 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