| First Author | Miller AT | Year | 2004 |
| Journal | Immunity | Volume | 21 |
| Issue | 1 | Pages | 67-80 |
| PubMed ID | 15345221 | Mgi Jnum | J:93606 |
| Mgi Id | MGI:3487208 | Doi | 10.1016/j.immuni.2004.06.009 |
| Citation | Miller AT, et al. (2004) Signaling through Itk promotes T helper 2 differentiation via negative regulation of T-bet. Immunity 21(1):67-80 |
| abstractText | 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. |
