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면역미생물공생연구단
면역 미생물 공생 연구단
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Transcriptional regulator CTR9 inhibits Th17 differentiation via repression of IL-17 expression

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Title
Transcriptional regulator CTR9 inhibits Th17 differentiation via repression of IL-17 expression
Author(s)
Yoo HS; Choi Y; Ahn N; Lee S; Kim WU; Min Seong Jang; Myoung Ho Jang; Kim YS; Yoo JY
Publication Date
2014-02
Journal
JOURNAL OF IMMUNOLOGY, v.192, no.4, pp.1440 - 1448
Publisher
AMER ASSOC IMMUNOLOGISTS
Abstract
PAF complex is an evolutionarily conserved transcriptional complex that associates with RNA polymerase II in the coding region of actively transcribing genes. Although its transcriptional activity is closely related to diverse cellular processes, such as cell-cycle progression or development in mammals, its role in immune responses has not been addressed yet. In this study, we show that CTR9, a component of PAF complex, functions as a repressor of Th17 differentiation. Both mRNA and protein levels of CTR9 were significantly decreased during the differentiation processes of naive T into Th17 effector cells. When CTR9 was depleted, IL-17 expression was induced and differentiation into Th17 cells enhanced. In naive T cells, CTR9 occupied the coding region of Il17a, but dissociated under Th17 in vitro-polarizing conditions. In contrast, both CDC73 and PAF1 were recruited to the Il17a locus under Th17-differentiation conditions. In the IL-6–stimulated splenocytes, expression of CTR9 was decreased, and chromatin-bound CTR9 disappeared in the coding region of Il17a. IL-6 also directly repressed expression of CTR9 gene, as promoter activity of CTR9 was similarly repressed by IL-6 treatment. Moreover, in mice with collagen-induced arthritis, lentivirus-mediated CTR9 overexpression in the joints ameliorated arthritis severity, decreasing the frequency of CD4+IL-17+ T cells in lymph nodes. In conclusion, our data propose a novel feed-forward loop of IL-17 transcriptional regulatory circuit, via IL-6–mediated repression of CTR9 which is a transcriptional repressor of IL-17. The Journal of Immunology, 2014, 192: 1440–1448. Copyright2014 by The American Association of Immunologists, Inc.
URI
https://pr.ibs.re.kr/handle/8788114/2368
ISSN
0022-1767
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
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