Signaling through Itk promotes T helper 2 differentiation via negative regulation of T-bet
Graduate School of Biomedical Sciences; Department of Pathology
Life Sciences | Medicine and Health Sciences
The Tec family tyrosine kinase, Itk, is critical for PLC-gamma1 activation downstream of the TCR. Studies of Itk-/- mice have demonstrated a requirement for Itk in Th2 cytokine production and protective immunity to parasitic infections. Here we address the mechanism by which Itk regulates Th2 differentiation. We find that naive Itk-/- CD4+ T cells respond normally to cytokine skewing signals and can differentiate efficiently into either Th1 or Th2 lineage cells. In the absence of skewing cytokines, wild-type CD4+ T cells stimulated with low-avidity ligands preferentially express GATA-3 mRNA and differentiate into Th2 cells. Under these same stimulation conditions, Itk-/- T cells produce large amounts of T-bet mRNA and differentiate into IFN-gamma-producing cells. Furthermore, Itk is upregulated during Th2 differentiation, while Rlk, a related Tec kinase, disappears rapidly from differentiating Th2 cells. Together, these findings provide a molecular explanation for the essential role of Itk in Th2 differentiation.
DOI of Published Version
Immunity. 2004 Jul;21(1):67-80. Link to article on publisher's site
Miller AT, Wilcox HM, Lai Z, Berg LJ. (2004). Signaling through Itk promotes T helper 2 differentiation via negative regulation of T-bet. GSBS Student Publications. https://doi.org/10.1016/j.immuni.2004.06.009. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/868