First Author | Kemp KL | Year | 2010 |
Journal | J Immunol | Volume | 184 |
Issue | 8 | Pages | 4178-84 |
PubMed ID | 20237292 | Mgi Jnum | J:159870 |
Mgi Id | MGI:4452572 | Doi | 10.4049/jimmunol.0901282 |
Citation | Kemp KL, et al. (2010) Lck mediates Th2 differentiation through effects on T-bet and GATA-3. J Immunol 184(8):4178-84 |
abstractText | The Src family kinase Lck has been shown to be crucial in T cell signaling and development. However, its role in Th effector functions is not well understood. Lck has previously been shown to play a role in the cytokine expression of Th2 cells, but the mechanism by which Lck influences Th2 effector functions is unknown. Using a mouse model, we report that Lck is important in regulating the expression of IL-4 in Th2 skewed cells but is not as necessary for the expression of Th2 cytokines IL-5, IL-10, and IL-13. Furthermore, in the absence of Lck, T-bet and GATA-3 expression is aberrant. Moreover, this atypical expression pattern of T-bet and GATA-3 correlates with increased histone 3 acetylation at the Ifng locus and production of the Th1 cytokine IFN-gamma. We find overexpression of GATA-3 restores IL-4 expression in lck(-/-) Th2 cells; this indicates that the decreased IL-4 expression is due in part to reduced amounts of GATA-3. Taken together, these data imply that Lck mediates Th2 differentiation through effects on T-bet and GATA-3. |