title: Gαq Regulates the Development of Rheumatoid Arthritis by Modulating Th1 Differentiation.
abstract: The Gαq-containing G protein, an important member ofGq/11class, is ubiquitously expressed in mammalian cells. Gαq has been found to play an important role in immune regulation and development of autoimmune disease such as rheumatoid arthritis (RA). However, how Gαq participates in the pathogenesis of RA is still not fully understood. In the present study, we aimed to find out whether Gαq controls RA via regulation of Th1 differentiation. We observed that the expression of Gαq was negatively correlated with the expression of signature Th1 cytokine (IFN-γ) in RA patients, which suggests a negative role of Gαq in differentiation of Th1 cells. By using Gαq knockout (Gnaq-/-) mice, we demonstrated that loss of Gαq led to enhanced Th1 cell differentiation. Gαq negative regulated the differentiation of Th1 cell by modulating the expression of T-bet and the activity of STAT4. Furthermore, we detected the increased ratio of Th1 cells inGnaq-/-bone marrow (BM) chimeras spontaneously developing inflammatory arthritis. In conclusion, results presented in the study demonstrate that loss of Gαq promotes the differentiation of Th1 cells and contributes to the pathogenesis of RA.
authors.affiliation: Molecular Biology Research Center, Key Medical Health Laboratory for Laboratory Medicine of Shandong Province, Department of Laboratory Medicine, Shandong Medical College, Linyi, Shandong 276000, China.
authors.forename: Dashan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, China.
authors.forename: Yan
authors.identifier: 0000-0002-4316-8298
authors.initials: Y
authors.lastname: He
authors.affiliation: Key Medical Health Laboratory for Laboratory Medicine of Shandong Province, Department of Laboratory Medicine, Shandong Medical College, Linyi, Shandong 276000, China.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, China.
authors.forename: Guixiu
authors.identifier: 0000-0003-4044-3394
authors.initials: G
authors.lastname: Shi
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001168:Arthritis / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000097:blood*; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; C494091:Stat4 protein, mouse; D043802:GTP-Binding Protein alpha Subunits, Gq-G11