title: Aberrant CD200/CD200R1 expression and its potential role in Th17 cell differentiation, chemotaxis and osteoclastogenesis in rheumatoid arthritis.
abstract: OBJECTIVE
  CD200/CD200R1 signalling has an immunoregulatory effect on the activation threshold of the inflammatory immune response and maintains immune homeostasis. In this study we evaluated the status of CD200/CD200R1 interaction in patients with RA.
  
  
  METHODS
  The expression of CD200 and CD200R1 was examined by immunohistochemistry and flow cytometry and was compared between RA patients and healthy controls (HCs). Sorted CD4(+) T cells were stained with carboxyfluorescein succinimidyl ester (CFSE) and annexin V-propidium iodide to evaluate the effect of CD200 on cell proliferation and apoptosis. The effect of CD200 on Th17 differentiation, function and osteoclastogenesis was determined by flow cytometry, transwell migration assay and immunocytochemistry, respectively.
  
  
  RESULTS
  The proportion of CD200(+) cells and CD200R1(+) cells in peripheral blood mononuclear cells, peripheral CD14(+) cells and CD4(+) T cells was significantly lower in the RA patients than in HCs, whereas the number of CD200(+) cells was higher in synovium from RA patients than in that from HCs. After treatment with infliximab and MTX we found increased expression of peripheral CD200/CD200R1 that correlated with a decrease in the 28-joint DAS. CD200Fc in vitro partially inhibited CD4(+) T cell proliferation, promoted CD4(+) T cell apoptosis, reduced CD4(+) T cell differentiation into Th17 cells and down-regulated CCR6-mediated Th17 chemotaxis in cells from RA patients. In addition, the engagement of the CD200 receptors on CD14(+) cells with CD200Fc in vitro reduced osteoclastogenesis and inhibited CD14(+) cell-driven Th17 differentiation.
  
  
  CONCLUSIONS
  Abnormal CD200/CD200R1 expression in RA may contribute to abnormal Th17 cell differentiation, chemotaxis and osteoclastogenesis.
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, Department of Health Care, China-Japan Friendship Hospital, Beijing, Department of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing and Department of Immunology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing, China. Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, Department of Health Care, China-Japan Friendship Hospital, Beijing, Department of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing and Department of Immunology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, Department of Health Care, China-Japan Friendship Hospital, Beijing, Department of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing and Department of Immunology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, Department of Health Care, China-Japan Friendship Hospital, Beijing, Department of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing and Department of Immunology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, Department of Health Care, China-Japan Friendship Hospital, Beijing, Department of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing and Department of Immunology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Leng
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, Department of Health Care, China-Japan Friendship Hospital, Beijing, Department of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing and Department of Immunology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, Department of Health Care, China-Japan Friendship Hospital, Beijing, Department of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing and Department of Immunology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, Department of Health Care, China-Japan Friendship Hospital, Beijing, Department of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing and Department of Immunology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Yongzhe
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, Department of Health Care, China-Japan Friendship Hospital, Beijing, Department of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing and Department of Immunology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, Department of Health Care, China-Japan Friendship Hospital, Beijing, Department of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing and Department of Immunology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Fengchun
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, Department of Health Care, China-Japan Friendship Hospital, Beijing, Department of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing and Department of Immunology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, Department of Health Care, China-Japan Friendship Hospital, Beijing, Department of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing and Department of Immunology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing, China. zxpumch2003@sina.com.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, Department of Health Care, China-Japan Friendship Hospital, Beijing, Department of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing and Department of Immunology, School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Sciences, Chinese Academy of Medical Science, Beijing, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement; D002633:Chemotaxis / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D064446:Orexin Receptors; D010010:Osteoclasts / Q000166:cytology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D018501:Antirheumatic Agents; C477337:CD200R1 protein, human; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; D000069285:Infliximab; C042739:antigens, CD200; D008727:Methotrexate
keywords: CD200/CD200R1; Th17 cells; osteoclastogenesis; rheumatoid arthritis