Felices, MartinYin, Catherine C.Kosaka, YokoKang, JoonsooBerg, Leslie J.2022-08-232022-08-232009-05-192010-04-07Proc Natl Acad Sci U S A. 2009 May 19;106(20):8308-13. <a href="http://dx.doi.org/10.1073/pnas.0808459106">Link to article on publisher's site</a>0027-8424 (Linking)10.1073/pnas.080845910619416854https://hdl.handle.net/20.500.14038/39410In conventional alphabeta T cells, the Tec family tyrosine kinase Itk is required for signaling downstream of the T cell receptor (TCR). Itk also regulates alphabeta T cell development, lineage commitment, and effector function. A well established feature of Itk(-/-) mice is their inability to generate T helper type 2 (Th2) responses that produce IL-4, IL-5, and IL-13; yet these mice have spontaneously elevated levels of serum IgE and increased numbers of germinal center B cells. Here we show that the source of this phenotype is gammadelta T cells, as normal IgE levels are observed in Itk(-/-)Tcrd(-/-) mice. When stimulated through the gammadelta TCR, Itk(-/-) gammadelta T cells produce high levels of Th2 cytokines, but diminished IFNgamma. In addition, activated Itk(-/-) gammadelta T cells up-regulate costimulatory molecules important for B cell help, suggesting that they may directly promote B cell activation and Ig class switching. Furthermore, we find that gammadelta T cells numbers are increased in Itk(-/-) mice, most notably the Vgamma1.1(+)Vdelta6.3(+) subset that represents the dominant population of gammadelta NKT cells. Itk(-/-) gammadelta NKT cells also have increased expression of PLZF, a transcription factor required for alphabeta NKT cells, indicating a common molecular program between alphabeta and gammadelta NKT cell lineages. Together, these data indicate that Itk signaling regulates gammadelta T cell lineage development and effector function and is required to control IgE production in vivo.en-US<p>Publisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/aboutpnas/authorfaq.xhtml.</p>AnimalsB-LymphocytesCell LineageCytokinesImmunoglobulin Class SwitchingImmunoglobulin ELymphocyte ActivationMiceMice, KnockoutNatural Killer T-CellsProtein-Tyrosine KinasesReceptors, Antigen, T-Cell, alpha-beta*Receptors, Antigen, T-Cell, gamma-deltaT-LymphocytesTh2 CellsImmunology and Infectious DiseaseJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3205&amp;context=oapubs&amp;unstamped=1https://escholarship.umassmed.edu/oapubs/22061264538oapubs/2206