| First Author | Schaeffer EM | Year | 2001 |
| Journal | Nat Immunol | Volume | 2 |
| Issue | 12 | Pages | 1183-8 |
| PubMed ID | 11702066 | Mgi Jnum | J:72934 |
| Mgi Id | MGI:2154016 | Doi | 10.1038/ni734 |
| Citation | Schaeffer EM, et al. (2001) Mutation of Tec family kinases alters T helper cell differentiation. Nat Immunol 2(12):1183-8 |
| abstractText | 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. |
