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

Kyeorda L. Kemp, Steven D. Levin, Paul J. Bryce, Paul L. Stein

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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-γ. 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.

Original languageEnglish (US)
Pages (from-to)4178-4184
Number of pages7
JournalJournal of Immunology
Volume184
Issue number8
DOIs
StatePublished - Apr 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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