title: Dopamine D2 Receptor Is Involved in Alleviation of Type II Collagen-Induced Arthritis in Mice.
abstract: Human and murine lymphocytes express dopamine (DA) D2-like receptors including DRD2, DRD3, and DRD4. However, their roles in rheumatoid arthritis (RA) are less clear. Here we showed that lymphocyte DRD2 activation alleviates both imbalance of T-helper (Th)17/T-regulatory (Treg) cells and inflamed symptoms in a mouse arthritis model of RA. Collagen-induced arthritis (CIA) was prepared by intradermal injection of chicken collagen type II (CII) in tail base of DBA/1 mice or Drd2 (-/-) C57BL/6 mice. D2-like receptor agonist quinpirole downregulated expression of proinflammatory Th17-related cytokines interleukin- (IL-) 17 and IL-22 but further upregulated expression of anti-inflammatory Treg-related cytokines transforming growth factor- (TGF-) β and IL-10 in lymphocytes in vitro and in ankle joints in vivo in CIA mice. Quinpirole intraperitoneal administration reduced both clinical arthritis score and serum anti-CII IgG level in CIA mice. However, Drd2 (-/-) CIA mice manifested more severe limb inflammation and higher serum anti-CII IgG level and further upregulated IL-17 and IL-22 expression and downregulated TGF-β and IL-10 expression than wild-type CIA mice. In contrast, Drd1 (-/-) CIA mice did not alter limb inflammation or anti-CII IgG level compared with wild-type CIA mice. These results suggest that DRD2 activation is involved in alleviation of CIA symptoms by amelioration of Th17/Treg imbalance.
authors.affiliation: Department of Physiology, School of Medicine and Co-Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Lu
authors.affiliation: Department of Physiology, School of Medicine and Co-Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, China.
authors.forename: Yi-Qian
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: Department of Physiology, School of Medicine and Co-Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, China.
authors.forename: Qiao-Wen
authors.initials: QW
authors.lastname: Deng
authors.affiliation: Department of Physiology, School of Medicine and Co-Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Peng
authors.affiliation: Department of Physiology, School of Medicine and Co-Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, China.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Qiu
mesh_terms: D000818:Animals; D000843:Ankle Joint / Q000378:metabolism / Q000473:pathology; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D017447:Receptors, Dopamine D1 / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D000097043:Interleukin-22
chemical_list: D016753:Interleukin-10; D020381:Interleukin-17; D007378:Interleukins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016212:Transforming Growth Factor beta; D000097043:Interleukin-22; C000600618:DRD2 protein, mouse; C583261:Drd1 protein, mouse