Involvement of GATA3 in protein kinase C theta-induced Th2 cytokine expression.
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.
Stevens
Lisa
L
Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT 06877, USA.
Htut
Tin M
TM
White
Della
D
Li
Xiang
X
Hanidu
Adedayo
A
Stearns
Carol
C
Labadia
Mark E
ME
Li
Jun
J
Brown
Maryanne
M
Yang
Jianfei
J
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D050990:GATA3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007527:Isoenzymes / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011493:Protein Kinase C / Q000502:physiology*; D000074121:Protein Kinase C-theta; D018418:Th2 Cells / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D007527:Isoenzymes; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta