c-Maf and JunB mediation of Th2 differentiation induced by the type 2 G protein-coupled receptor (VPAC2) for vasoactive intestinal peptide.
Vasoactive intestinal peptide and its G protein-coupled receptors, VPAC(1) and VPAC(2), regulate critical aspects of innate and adaptive immunity. T cell VPAC(2)Rs mediate changes in cytokine generation, which potently increase the Th2/Th1 ratio and consequently shift the effector responses toward allergy and inflammation. To examine mechanisms of VPAC(2) promotion of the Th2 phenotype, we analyzed controls of IL-4 transcription in CD4 T cells from T cell-targeted VPAC(2) transgenic (Tg), VPAC(2) knockout, and wild-type (WT) mice. c-maf and junB mRNA, protein, and activity were significantly up-regulated to a higher level in TCR-stimulated CD4 T cells from Tg mice compared with those from knockout and WT C57BL/6 mice. In contrast, GATA3, T-bet, and NFATc levels were identical in WT and Tg CD4 T cells. Vasoactive intestinal peptide binding to VPAC(2) on CD4 T cells specifically induces an up-regulation of the Th2-type transcription factors c-Maf and JunB, which consequently enhances IL-4 and IL-5 production, leading to a Th2-type phenotype.
Voice
Julia
J
Departments of Medicine and Microbiology/Immunology, Medical Center, University of California-San Francisco, 533 Parnassus at 4th, San Francisco, CA 94143, USA.
Donnelly
Samantha
S
Dorsam
Glenn
G
Dolganov
Gregory
G
Paul
Sudhir
S
Goetzl
Edward J
EJ
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000502:physiology*; D051257:Proto-Oncogene Proteins c-maf; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D018418:Th2 Cells / Q000166:cytology*; D015854:Up-Regulation; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D015848:Interleukin-5; C495607:MAF protein, human; C495608:Maf protein, mouse; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D051257:Proto-Oncogene Proteins c-maf; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D015847:Interleukin-4; D014660:Vasoactive Intestinal Peptide