The SWI/SNF chromatin-remodeling complex modulates peripheral T cell activation and proliferation by controlling AP-1 expression.
The SWI/SNF chromatin-remodeling complex has been implicated in the activation and proliferation of T cells. After T cell receptor signaling, the SWI/SNF complex rapidly associates with chromatin and controls gene expression in T cells. However, the process by which the SWI/SNF complex regulates peripheral T cell activation has not been elucidated. In this study, we show that the SWI/SNF complex regulates cytokine production and proliferation of T cells. During T cell activation, the SWI/SNF complex is recruited to the promoter of the transcription factor AP-1, and it increases the expression of AP-1. Increased expression of the SWI/SNF complex resulted in enhanced AP-1 activity, cytokine production, and proliferation of peripheral T cells, whereas knockdown of the SWI/SNF complex expression impaired the AP-1 expression and reduced the activation and proliferation of T cells. Moreover, mice that constitutively expressed the SWI/SNF complex in T cells were much more susceptible to experimentally induced autoimmune encephalomyelitis than the normal mice were. These results suggest that the SWI/SNF complex plays a critical role during T cell activation and subsequent immune responses.
Jeong
Seung Min
SM
Department of Biological Sciences, Institute of Molecular Biology and Genetics, and Research Center for Functional Cellulomics, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-742, Korea.
Lee
Changjin
C
Lee
Sung Kyu
SK
Kim
Jieun
J
Seong
Rho Hyun
RH
D000818:Animals; D018801:CD2 Antigens / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D016762:Genes, fos / Q000502:physiology; D016758:Genes, jun / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D018801:CD2 Antigens; D016207:Cytokines; C491090:Smarcc1 protein, mouse; D018808:Transcription Factor AP-1; D014157:Transcription Factors