Deficiency of the G protein G alpha q ameliorates experimental autoimmune encephalomyelitis with impaired DC-derived IL-6 production and Th17 differentiation
文献类型：期刊论文
| 作者 | Lai, Weiming2; Cai, Yingying2; Zhou, Jinfeng2; Chen, Shuai2; Qin, Chaoyan2; Yang, Cuixia2; Liu, Junling3; Xie, Xin4 ; Du, Changsheng1,2
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| 刊名 | CELLULAR & MOLECULAR IMMUNOLOGY
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| 出版日期 | 2017-06 |
| 卷号 | 14期号:6页码:557-567 |
| 关键词 | Dendritic cells EAE G alpha q IL-6 Th17 differentiation MS |
| ISSN号 | 1672-7681 |
| DOI | 10.1038/cmi.2016.65 |
| 文献子类 | Article |
| 英文摘要 | Many G protein-coupled receptors (GPCRs) are reported to be involved in the pathogenesis of multiple sclerosis (MS), and similar to 40% of all identified GPCRs rely on the G alpha q/11 G protein family to stimulate inositol lipid signaling. However, the function of G alpha subunits in MS pathogenesis is still unknown. In this study, we attempted to determine the role of Gaq in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a well-known mouse model of MS. We discovered that compared with wild-type mice, G alpha q-knockout mice exhibited less severe EAE symptoms, with lower clinical scores, reduced leukocyte infiltration and less extensive demyelination. Moreover, a significantly lower percentage of Th17 cells, one of the key players in MS pathogenesis, was observed in Gaq-knockout EAE mice. Studies in vitro demonstrated that deficiency of Gaq in CD4(+) T cells directly impaired Th17 differentiation. In addition, deficiency of Gaq significantly impaired DC-derived IL-6 production, thus inhibiting Th17 differentiation and the G alpha q-PLC beta-PKC and Gaq-MAPKs signaling pathways involved in the reduced IL-6 production by DCs. In summary, our data highlighted the critical role of G alpha q in regulating Th17 differentiation and MS pathogenesis. |
| WOS关键词 | ENVIRONMENTAL RISK-FACTORS ; CENTRAL-NERVOUS-SYSTEM ; MULTIPLE-SCLEROSIS ; CELL-DIFFERENTIATION ; RECEPTORS COUPLE ; PGE(2) RECEPTORS ; TYROSINE KINASE ; DENDRITIC CELLS ; MURINE LUPUS ; T-CELLS |
| 资助项目 | Ministry of Science and Technology of China[2014CB541903] ; Ministry of Science and Technology of China[2012CB910404] ; National Natural Science Foundation of China[31171348] ; National Natural Science Foundation of China[31371414] ; Shanghai Municipal Education Commission[14zz042] ; State Key Laboratory of Drug Research[SIMM1302KF-09] ; Fundamental Research Funds for the Central Universities[00000000] |
| WOS研究方向 | Immunology |
| 语种 | 英语 |
| CSCD记录号 | CSCD:6049369 |
| WOS记录号 | WOS:000402654200009 |
| 出版者 | CHIN SOCIETY IMMUNOLOGY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272648]  |
| 专题 | 国家新药筛选中心 |
| 通讯作者 | Du, Changsheng |
| 作者单位 | 1.Tongji Univ, Shanghai Key Lab Signaling & Dis Res, Sch Life Sci & Technol, 1239 Si Ping Rd, Shanghai 200092, Peoples R China 2.Tongji Univ, Dept Cent Lab, Shanghai Peoples Hosp 10, Sch Life Sci & Technol, Shanghai 200092, Peoples R China; 3.Shanghai Jiao Tong Univ, Dept Biochem & Mol Cell Biol, Sch Med, Shanghai 200025, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Lai, Weiming,Cai, Yingying,Zhou, Jinfeng,et al. Deficiency of the G protein G alpha q ameliorates experimental autoimmune encephalomyelitis with impaired DC-derived IL-6 production and Th17 differentiation[J]. CELLULAR & MOLECULAR IMMUNOLOGY,2017,14(6):557-567. |
| APA | Lai, Weiming.,Cai, Yingying.,Zhou, Jinfeng.,Chen, Shuai.,Qin, Chaoyan.,...&Du, Changsheng.(2017).Deficiency of the G protein G alpha q ameliorates experimental autoimmune encephalomyelitis with impaired DC-derived IL-6 production and Th17 differentiation.CELLULAR & MOLECULAR IMMUNOLOGY,14(6),557-567. |
| MLA | Lai, Weiming,et al."Deficiency of the G protein G alpha q ameliorates experimental autoimmune encephalomyelitis with impaired DC-derived IL-6 production and Th17 differentiation".CELLULAR & MOLECULAR IMMUNOLOGY 14.6(2017):557-567. |
入库方式： OAI收割
来源：上海药物研究所
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