Galpha12 is critical for TCR-induced IL-2 production and differentiation of T helper 2 and T helper 17 cells.
G12 family have been known to modulate a variety of cellular events such as cell migration, B cell activation and maturation, cytokine production, and cell differentiation. In particular, Galpha12 modulates IgG production, thus induces IgG antibody-mediated immune responses. However, it is largely unknown whether Galpha12 is required for T cell-mediated immune functions. In this study, we investigated the effects of Galpha12 in the activation and differentiation of CD4+ T cells. While PMA plus ionomycin induced equal levels of IL-2 production in WT and Galpha12-deficient lymphocytes, TCR-triggered IL-2 production was significantly attenuated in Galpha12 KO lymphocytes. In particular, CD4+ T cells and effector Th cells lacking of Galpha12 revealed diminished IL-2 production, but not IFNgamma production, upon TCR stimulation. In addition, supplement of IL-2 preferentially induced Galpha12-deficient CD4+ T cells into Th2 and Th17 cells; however, the expression of specific transcription factors was unchanged in Galpha12 KO Th cells. While IL-2 expression was still diminished by the re-stimulation with anti-CD3, PMA plus ionomycin restored IL-2 production in Galpha12-deficient Th1 and Th2 cells. These results suggest that Galpha12 may be a critical signaling molecule in TCR-induced IL-2 production and also relay a signal to suppress Th2 and Th17 cell differentiation.
College of Pharmacy, Division of Life and Pharmaceutical Sciences and Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul 120-750, Republic of Korea.
Hee Yeon
HY
Won
Hyun Jung
HJ
Min
Woo Hyung
WH
Lee
Sang Geon
SG
Kim
Eun Sook
ES
Hwang
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D002454:Cell Differentiation; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D015704:CD4 Antigens; D020381:Interleukin-17; D007376:Interleukin-2; D007371:Interferon-gamma; D044365:GTP-Binding Protein alpha Subunits, G12-G13