Overexpression of CIITA in T cells aggravates Th2-mediated colitis in mice.
The MHC class II transactivator (CIITA) is the master transcriptional regulator of genes involved in MHC class II restricted antigen presentation. Previously we suggested another role of CIITA in Th1/Th2 balance by demonstrating that forced expression of CIITA in murine T cells repressed Th1 immunity both in vitro and in vivo. However, the results were contradictory to the report that CIITA functioned to suppress the production of Th2 cytokine by CD4+ T cells in CIITA deficient mice. In this study, we investigated the influence of constitutive expression of CIITA in T cells on Th2 immune response in vivo using murine experimental colitis model. In the dextran sodium sulfate-induced acute colitis, a disease involving innate immunity, CIITA transgenic mice and wild type control mice showed similar progression of the disease. However, the development of oxazolone-induced colitis, a colitis mediated by predominantly Th2 immune response, was aggravated in CIITA-transgenic mice. And, CD4+ T cells from the mesenteric lymph node of CIITA-transgenic mice treated with oxazolone exhibited a high level of IL-4 secretion. Together, these data demonstrate that constitutive expression of CIITA in T cells skews immune response to Th2, resulting in aggravation of Th2-mediated colitis in vivo.
Kim
Tae Woon
TW
Department of Pathology, Hallym University College of Medicine, Chuncheon, Korea.
Park
Hyo Jin
HJ
Choi
Eun Young
EY
Jung
Kyeong Cheon
KC
D000818:Animals; D003092:Colitis / Q000209:etiology*; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000502:physiology*; D010081:Oxazolone / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology*
C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D010081:Oxazolone; D015847:Interleukin-4