| First Author | Cannons JL | Year | 2004 |
| Journal | Immunity | Volume | 21 |
| Issue | 5 | Pages | 693-706 |
| PubMed ID | 15539155 | Mgi Jnum | J:93887 |
| Mgi Id | MGI:3510075 | Doi | 10.1016/j.immuni.2004.09.012 |
| Citation | Cannons JL, et al. (2004) SAP regulates T(H)2 differentiation and PKC-theta-mediated activation of NF-kappaB1. Immunity 21(5):693-706 |
| abstractText | XLP is caused by mutations affecting SAP, an adaptor that recruits Fyn to SLAM family receptors. SAP-deficient mice recapitulate features of XLP, including increased T cell activation and decreased humoral responses post-infection. SAP-deficient T cells also show increased TCR-induced IFN-gamma and decreased T(H)2 cytokine production. We demonstrate that the defect in IL-4 secretion in SAP-deficient T cells is independent of increased IFN-gamma production. SAP-deficient cells respond normally to polarizing cytokines, yet show impaired TCR-mediated induction of GATA-3 and IL-4. Examination of TCR signaling revealed normal Ca(2+) mobilization and ERK activation in SAP-deficient cells, but decreased PKC-theta recruitment, Bcl-10 phosphorylation, IkappaB-alpha degradation, and nuclear NF-kappaB1/p50 levels. Similar defects were observed in Fyn-deficient cells. SLAM engagement amplified PKC-theta recruitment in wt but not SAP- or Fyn-deficient cells, arguing that a SAP/Fyn-mediated pathway enhances PKC-theta/NF-kappaB1 activation and suggesting a role for this pathway in T(H)2 regulation. |
