Signaling through Itk promotes T helper 2 differentiation via negative regulation of T-bet
KeywordsAnimals; CD4-Positive T-Lymphocytes; Cell Differentiation; *Gene Expression Regulation; Mice; Protein-Tyrosine Kinases; *Signal Transduction; T-Box Domain Proteins; Th1 Cells; Th2 Cells; Transcription Factors
Medicine and Health Sciences
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AbstractThe 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.
SourceImmunity. 2004 Jul;21(1):67-80. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/34211
Related ResourcesLink to article in PubMed