Document Detail


Sox5 and c-Maf cooperatively induce Th17 cell differentiation via RORγt induction as downstream targets of Stat3.
MedLine Citation:
PMID:  25073789     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Stat3 signaling is essential for the induction of RORγt and subsequent Th17 cell differentiation. However, the downstream targets of Stat3 for RORγt expression remain largely unknown. We show here that a novel isoform of Sox5, named Sox5t, is induced in Th17 cells in a Stat3-dependent manner. In vivo, T cell-specific Sox5-deficient mice exhibit impaired Th17 cell differentiation and are resistant to experimental autoimmune encephalomyelitis and delayed-type hypersensitivity. Retrovirus-mediated induction of Sox5 together with c-Maf induces Th17 cell differentiation even in Stat3-deficient CD4(+) T cells but not in RORγt-deficient CD4(+) T cells, indicating that Sox5 and c-Maf induce Th17 cell differentiation as downstream effectors of Stat3 and as upstream inducers of RORγt. Moreover, Sox5 physically associates with c-Maf via the HMG domain of Sox5 and DNA-binding domain of c-Maf, and Sox5 together with c-Maf directly activates the promoter of RORγt in CD4(+) T cells. Collectively, our results suggest that Sox5 and c-Maf cooperatively induce Th17 cell differentiation via the induction of RORγt as downstream targets of Stat3.
Authors:
Shigeru Tanaka; Akira Suto; Taro Iwamoto; Daisuke Kashiwakuma; Shin-Ichiro Kagami; Kotaro Suzuki; Hiroaki Takatori; Tomohiro Tamachi; Koichi Hirose; Atsushi Onodera; Junpei Suzuki; Osamu Ohara; Masakatsu Yamashita; Toshinori Nakayama; Hiroshi Nakajima
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-29
Journal Detail:
Title:  The Journal of experimental medicine     Volume:  -     ISSN:  1540-9538     ISO Abbreviation:  J. Exp. Med.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985109R     Medline TA:  J Exp Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2014 Tanaka et al.
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