title: Involvement of P2X7 receptor signaling on regulating the differentiation of Th17 cells and type II collagen-induced arthritis in mice.
abstract: Interleukin (IL)-17 producing T helper (Th17) cells are major effector cells in the pathogenesis of rheumatoid arthritis (RA). The P2X7 receptor (P2X7R) has emerged as a potential site in the regulation of inflammation in RA but little is known of its functional role on the differentiation of Th17 cells. This study investigates the in vitro and in vivo effects of P2X7R on Th17 cell differentiation during type II collagen (CII) induced experimental arthritis model. In CII-treated dendritic cells (DCs) and DC/CD4+T coculture system, pretreatment with pharmacological antagonists of P2X7R (Suramin and A-438079) caused strong inhibition of production of Th17-promoting cytokines (IL-1β, TGF-β1, IL-23p19 and IL-6). Exposure to CII induced the elevation of mRNAs encoding retinoic acid receptor-related orphan receptor α and γt, which were abolished by pretreatment with P2X7R antagonists. Furthermore, blocking P2X7R signaling abolished the CII-mediated increase in IL-17A. Blockade of P2X7R remarkably inhibited hind paw swelling and ameliorated pathological changes in ankle joint of the collagen-induced arthritis mice. Thus, we demonstrated a novel function for P2X7R signaling in regulating CII-induced differentiation of Th17 cells. P2X7R signaling facilitates the development of the sophisticated network of DC-derived cytokines that favors a Th17 phenotype.
authors: Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, No. 72 Guangzhou Road, Nanjing, Jiangsu Province 210008, China.
authors: Zhi-Dan
authors: ZD
authors: Fan
authors: Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, No. 72 Guangzhou Road, Nanjing, Jiangsu Province 210008, China.
authors: Ya-Yuan
authors: YY
authors: Zhang
authors: Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, No. 72 Guangzhou Road, Nanjing, Jiangsu Province 210008, China.
authors: Yi-Hong
authors: YH
authors: Guo
authors: Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, No. 72 Guangzhou Road, Nanjing, Jiangsu Province 210008, China.
authors: Na
authors: N
authors: Huang
authors: Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, No. 72 Guangzhou Road, Nanjing, Jiangsu Province 210008, China.
authors: Hui-Hui
authors: HH
authors: Ma
authors: Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, No. 72 Guangzhou Road, Nanjing, Jiangsu Province 210008, China.
authors: Hui
authors: H
authors: Huang
authors: Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, No. 72 Guangzhou Road, Nanjing, Jiangsu Province 210008, China.
authors: Hai-Guo
authors: HG
authors: Yu
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001171:Arthritis, Juvenile / Q000378:metabolism* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation; D002648:Child; D024043:Collagen Type II / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008811:Mice, Inbred DBA; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D058504:Th17 Cells / Q000378:metabolism / Q000473:pathology*
chemical_list: D024043:Collagen Type II; D016207:Cytokines; C546468:P2RX7 protein, human; D058920:Purinergic P2X Receptor Antagonists; D058486:Receptors, Purinergic P2X7