NDLI: Transcriptional regulator CTR9 inhibits Th17 differentiation via repression of IL-17 expression.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lee, Saseong Kim, Yon Su Ahn, Narae Yoo, Hyeon-Seok Jang, Min Seong Yoo, Joo-Yeon Choi, Yongwook Jang, Myoung Ho Kim, Wan-Uk
Description	Author Affiliation: Yoo HS ( Division of Molecular and Life Sciences, Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea)
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.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-02-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Differentiation Genetics Gene Expression Regulation Interleukin-17 Interleukin-6 Metabolism Nuclear Proteins Phosphoproteins Th17 Cells Cytology Animals Arthritis, Experimental Carrier Proteins Lymph Nodes Immunology Mice Mice, Inbred C57bl Mice, Inbred Dba Promoter Regions, Genetic Protein Binding Rna, Messenger Biosynthesis Stat3 Transcription Factor Spleen Tumor Suppressor Proteins Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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