Yan Ren1, Bo Yang2, Yufeng Yin2, Xiaomei Leng2, Ying Jiang2, Lei Zhang2, Yongzhe Li2, Xin Li2, Fengchun Zhang2, Wei He2, Xuan Zhang3, Xuetao Cao2. 1. 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. 2. 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. 3. 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.
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. CONCLUSION: Abnormal CD200/CD200R1 expression in RA may contribute to abnormal Th17 cell differentiation, chemotaxis and osteoclastogenesis.
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 RApatients 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 RApatients than in HCs, whereas the number of CD200(+) cells was higher in synovium from RApatients 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 RApatients. In addition, the engagement of the CD200 receptors on CD14(+) cells with CD200Fc in vitro reduced osteoclastogenesis and inhibited CD14(+) cell-driven Th17 differentiation. CONCLUSION: Abnormal CD200/CD200R1 expression in RA may contribute to abnormal Th17 cell differentiation, chemotaxis and osteoclastogenesis.
Authors: Paulina A García-González; Katina Schinnerling; Alejandro Sepúlveda-Gutiérrez; Jaxaira Maggi; Lorena Hoyos; Rodrigo A Morales; Ahmed M Mehdi; Hendrik J Nel; Lilian Soto; Bárbara Pesce; María Carmen Molina; Miguel Cuchacovich; Milton L Larrondo; Óscar Neira; Diego Francisco Catalán; Catharien M Hilkens; Ranjeny Thomas; Ricardo A Verdugo; Juan C Aguillón Journal: Front Immunol Date: 2016-10-25 Impact factor: 7.561