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    
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.
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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