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Deficiency of the G protein Gαq ameliorates experimental autoimmune encephalomyelitis with impaired DC-derived IL-6 production and Th17 differentiation

Cellular & Molecular Immunology volume 14, pages 557–567 (2017)Cite this article

Abstract

Many G protein-coupled receptors (GPCRs) are reported to be involved in the pathogenesis of multiple sclerosis (MS), and ~40% of all identified GPCRs rely on the Gαq/11 G protein family to stimulate inositol lipid signaling. However, the function of Gα subunits in MS pathogenesis is still unknown. In this study, we attempted to determine the role of Gαq in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a well-known mouse model of MS. We discovered that compared with wild-type mice, Gαq-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 Gαq-knockout EAE mice. Studies in vitro demonstrated that deficiency of Gαq in CD4+ T cells directly impaired Th17 differentiation. In addition, deficiency of Gαq significantly impaired DC-derived IL-6 production, thus inhibiting Th17 differentiation and the Gαq-PLCβ-PKC and Gαq-MAPKs signaling pathways involved in the reduced IL-6 production by DCs. In summary, our data highlighted the critical role of Gαq in regulating Th17 differentiation and MS pathogenesis.

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Acknowledgements

This work was supported by grants from the Ministry of Science and Technology of China (2014CB541903, 2012CB910404), the National Natural Science Foundation of China (31171348, 31371414), the Shanghai Municipal Education Commission (14zz042), the State Key Laboratory of Drug Research (SIMM1302KF-09) and the Fundamental Research Funds for the Central Universities.

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  1. Weiming Lai and Yingying Cai: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China

    Weiming Lai, Yingying Cai, Jinfeng Zhou, Shuai Chen, Chaoyan Qin, Cuixia Yang & Changsheng Du

  2. Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Junling Liu

  3. National Center for Drug Screening, CAS Key Laboratory of Receptor Research, Chinese Academy of Sciences, Shanghai Institute of Materia Medica, Shanghai, 201203, China

    Xin Xie

  4. Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China

    Changsheng Du

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  1. Weiming Lai
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Lai, W., Cai, Y., Zhou, J. et al. Deficiency of the G protein Gαq ameliorates experimental autoimmune encephalomyelitis with impaired DC-derived IL-6 production and Th17 differentiation. Cell Mol Immunol 14, 557–567 (2017). https://doi.org/10.1038/cmi.2016.65

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