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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Mutation of Tec family kinases alters T helper cell differentiation.

The Tec kinases Rlk and Itk are critical for full T cell receptor (TCR)- induced activation of phospholipase C-gamma and mitogen-activated protein kinase. We show here that the mutation of Rlk and Itk impaired activation of the transcription factors NFAT and AP-1 and production of both T helper type 1 (TH1) and TH2 cytokines. Consistent with these biochemical defects, Itk-/- mice did not generate effective TH2 responses when challenged with Schistosoma mansoni eggs. Paradoxically, the more severely impaired Rlk-/-Itk-/- mice were able to mount a TH2 response and produced TH2 cytokines in response to this challenge. In addition, Rlk-/-Itk-/- cells showed impaired TCR-induced repression of the TH2-inducing transcription factor GATA-3, suggesting a potential mechanism for TH2 development in these hyporesponsive cells. Thus, mutations that affect Tec kinases lead to complex alterations in CD4+ TH cell differentiation.[1]


  1. Mutation of Tec family kinases alters T helper cell differentiation. Schaeffer, E.M., Yap, G.S., Lewis, C.M., Czar, M.J., McVicar, D.W., Cheever, A.W., Sher, A., Schwartzberg, P.L. Nat. Immunol. (2001) [Pubmed]
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