title: Metformin attenuates experimental autoimmune arthritis through reciprocal regulation of Th17/Treg balance and osteoclastogenesis.
abstract: Metformin is widely used to suppress certain functions of the cells found in diseases including diabetes and obesity. In this study, the effects of metformin on downregulating IL-17-producing T (Th17) cells, activating and upregulating regulatory T (Treg) cells, suppressing osteoclastogenesis, and clinically scoring collagen-induced arthritis (CIA) were investigated. To evaluate the effect of metformin on CIA, mice were orally fed with either metformin or saline as control three times a week for nine weeks. Histological analysis of the joints was performed using immunohistochemistry and Th17 cells and Treg cells of the spleen tissue were examined by confocal microscopy staining. Metformin mitigated the severity of CIA, reduced serum immunoglobulin concentrations, and reciprocally regulated Th17/Treg axis. Also, metformin treatment of normal cells cultured in Th17 conditions decreased the number of Th17 cells and increased the number of Treg cells. Metformin decreased gene expression and osteoclastogenic activity in CIA and normal mice. These results indicate that metformin had immunomodulatory actions influencing anti-inflammatory action on CIA through the inhibition of Th17 cell differentiation and the upregulation of Treg cell differentiation along with the suppression of osteoclast differentiation. Our results suggest that metformin may be a potential therapeutic for rheumatoid arthritis.
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea ; Laboratory of Immune Network, Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Son
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
authors.forename: Jennifer
authors.identifier: 0000-0001-6873-6629
authors.initials: J
authors.lastname: Lee
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea ; Laboratory of Immune Network, Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
authors.forename: Seon-Yeong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea ; Laboratory of Immune Network, Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea ; Laboratory of Immune Network, Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Park
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea ; Division of Rheumatology, Department of Internal Medicine, Konkuk University School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Kyoung-Woon
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea ; Laboratory of Immune Network, Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea ; Department of Life Science, College of Medicine, Laboratory of Immune Network, Rheumatism Research Center, Catholic Institutes of Medical Science, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D058504:Th17 Cells / Q000187:drug effects*
chemical_list: D020381:Interleukin-17; D008687:Metformin