Involvement of GATA3 in Protein Kinase C θ‐induced Th2 cytokine expression

Abstract

Protein kinase C theta (PKCtheta) is essential for T cell activation, as it is required for the activation of NF-kappaB and expression of IL-2. PKCtheta has also been shown to affect NFAT activation and Th2 differentiation. To better understand the role of PKCtheta in the regulation of T helper cells, we used PKCtheta-deficient DO11.10 transgenic T cells to study its role in vitro. DO11.10 Th1 cells deficient in PKCtheta produced significantly less TNF-alpha and IL-2. The expression of Th2 cytokines, including IL-4, IL-5, IL-10, IL-13 and IL-24 was significantly reduced in PKCtheta-deficient T cells. Moreover, the expression of the Th2 transcription factor, GATA3, was significantly reduced in PKCtheta-deficient T cells. Overexpression of GATA3 by retroviral infection in PKCtheta-deficient T cells resulted in increased expansion of IL-4-producing T cells and higher IL-4 production than that of wild type Th2 cells. IL-5, IL-10, IL-13 and IL-24 expressions were also rescued by GATA3 overexpression. Our observations suggest that PKCtheta regulates Th2 cytokine expression via GATA3.

ProtectiveToxoplasma gondii-Specific T-Cell Responses Require T-Cell-Specific Expression of Protein Kinase C-Theta

“…These data extend previous in vitro observations for anti-CD3/CD28-stimulated CD4 T cells, which also revealed that PKC-is involved in the upregulation of GATA3 (43). In addition, Th2 differentiation of Leishmania and Nippostrongylus brasiliensis-specific CD4 T cells is PKC-dependent (27).…”

The Serine-threonine Kinase Inositol-requiring Enzyme 1α (IRE1α) Promotes IL-4 Production in T Helper Cells

“…49). Moreover, PKC promotes Th2 cytokine expression (47,50). It is conceivable that IRE1␣ contributes to the TCR-induced PKC activation of IL-4.…”

Initiation and maintenance of Th2 cell identity

“…In addition, protein kinase C (PKC) u appears to regulate NF-kB activation and GATA3 expression. In PKCu-deficient CD4 T cells, the expression of GATA3 was severely impaired and Th2 cytokine production decreased [27]. Moreover, PKCu was reported to be a downstream target of Notch3 [28].…”