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Publication : Lck mediates Th2 differentiation through effects on T-bet and GATA-3.

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.
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