IR@PKUHSC  > 北京大学公共卫生学院  > 毒理学系
学科主题公共卫生
CDK inhibitors suppress Th17 and promote iTreg differentiation, and ameliorate experimental autoimmune encephalomyelitis in mice
Yoshida, Hideyuki1,2; Kotani, Hitoshi1,2; Kondo, Taisuke1,2; Tani, Ito1,2; Wei, Xuetao1,2,3; Tsuruta, Sanae1,2; Kimura, Akihiro1,2; Asakawa, Mayako1,2; Ito, Minako1,2; Nagai, Shigenori1,2; Yoshimura, Akihiko1,2
关键词Helper t Cells Cytokine Signaling Th17 Cdk
刊名BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
2013-06-07
DOI10.1016/j.bbrc.2013.04.096
435期:3页:378-384
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Biophysics
资助者Ministry of Education, Culture, Sports, Science and Technology, Tokyo ; Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP ; SENSHIN Research Foundation ; Kanae Foundation for the Promotion of Medical Science ; Mochida Memorial Foundation ; Uehara Memorial Foundation ; Takeda Science Foundation ; Ministry of Education, Culture, Sports, Science and Technology of Japan ; Ministry of Education, Culture, Sports, Science and Technology, Tokyo ; Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP ; SENSHIN Research Foundation ; Kanae Foundation for the Promotion of Medical Science ; Mochida Memorial Foundation ; Uehara Memorial Foundation ; Takeda Science Foundation ; Ministry of Education, Culture, Sports, Science and Technology of Japan
研究领域[WOS]Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]DEPENDENT KINASE INHIBITORS ; REGULATORY T-CELLS ; GROWTH-FACTOR-BETA ; ROR-GAMMA-T ; TGF-BETA ; RHEUMATOID-ARTHRITIS ; PHOSPHORYLATION ; T(H)17 ; TRANSCRIPTION ; GENERATION
英文摘要

Th17 cells, which have been implicated in autoimmune diseases, require IL-6 and TGF-beta for early differentiation. Several Smad-independent pathways including the JNK and the RhoA-ROCK pathways have been implicated in the induction of ROR gamma t, the master regulator of Th17, however, molecular mechanisms underlying Smad-independent pathway remain largely unknown. To identify novel pathways involved in Th17 differentiation, we screened 285 chemical inhibitors for known signaling pathways. Among them, we found that Kenpaullone, a GSK3-beta and CDK inhibitor, efficiently suppressed TGF-beta-mediated ROR gamma t induction and enhanced Foxp3 induction in primary T cells. Another CDK inhibitor, Roscovitine, but not other GSK3-beta inhibitors, suppressed Th17 differentiation and enhanced iTreg development. Kenpaullone and Roscovitine suppressed experimental autoimmune encephalomyelitis (EAE), a typical Th17-mediated autoimmune disease model. These two compounds enhanced STAT5 phosphorylation and restored IL-2 production in the presence of TGF-beta. These data suggest that CDK inhibitors modulate TGF-beta-signaling pathways, which restore TGF-beta-mediated suppression of IL-2 production, thereby modifying the Th17/iTreg balance. (C) 2013 Elsevier Inc. All rights reserved.

语种英语
所属项目编号22-4
资助者Ministry of Education, Culture, Sports, Science and Technology, Tokyo ; Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP ; SENSHIN Research Foundation ; Kanae Foundation for the Promotion of Medical Science ; Mochida Memorial Foundation ; Uehara Memorial Foundation ; Takeda Science Foundation ; Ministry of Education, Culture, Sports, Science and Technology of Japan ; Ministry of Education, Culture, Sports, Science and Technology, Tokyo ; Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP ; SENSHIN Research Foundation ; Kanae Foundation for the Promotion of Medical Science ; Mochida Memorial Foundation ; Uehara Memorial Foundation ; Takeda Science Foundation ; Ministry of Education, Culture, Sports, Science and Technology of Japan
WOS记录号WOS:000320904900010
Citation statistics
Cited Times:8[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52024
Collection北京大学公共卫生学院_毒理学系
作者单位1.Keio Univ, Sch Med, Dept Microbiol & Immunol, Shinjuku Ku, Tokyo 1608582, Japan
2.Japan Sci & Technol Agcy JST, CREST, Chiyoda Ku, Tokyo 1020075, Japan
3.Peking Univ, Sch Publ Hlth, Dept Toxicol, Beijing 100191, Peoples R China
Recommended Citation
GB/T 7714
Yoshida, Hideyuki,Kotani, Hitoshi,Kondo, Taisuke,et al. CDK inhibitors suppress Th17 and promote iTreg differentiation, and ameliorate experimental autoimmune encephalomyelitis in mice[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2013,435(3):378-384.
APA Yoshida, Hideyuki.,Kotani, Hitoshi.,Kondo, Taisuke.,Tani, Ito.,Wei, Xuetao.,...&Yoshimura, Akihiko.(2013).CDK inhibitors suppress Th17 and promote iTreg differentiation, and ameliorate experimental autoimmune encephalomyelitis in mice.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,435(3),378-384.
MLA Yoshida, Hideyuki,et al."CDK inhibitors suppress Th17 and promote iTreg differentiation, and ameliorate experimental autoimmune encephalomyelitis in mice".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 435.3(2013):378-384.
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