title: Aberrant CD200/CD200R1 expression and function in systemic lupus erythematosus contributes to abnormal T-cell responsiveness and dendritic cell activity.
abstract: BACKGROUND
  CD200 is a type I transmembrane glycoprotein that can regulate the activation threshold of inflammatory immune responses, polarize cytokine production, and maintain immune homeostasis. We therefore evaluated the functional status of CD200/CD200 receptor 1 (CD200R1) interactions in subjects with systemic lupus erythematosus (SLE).
  
  
  METHODS
  Serum CD200 level was detected by ELISA. The expression of CD200/CD200R1 by CD4+ T cells and dendritic cells (DCs) was examined by flow cytometry, and then compared between SLE patients and healthy controls. Peripheral blood mononuclear cells were stained with carboxyfluorescein diacetate succinimidyl ester and annexin V/propidium iodide for evaluation of the effect of CD200 on cell proliferation and apoptosis. In addition, the effect of CD200 on DC function was determined by transwell migration assay as well as by measurement of binding and phagocytosis of apoptotic cells.
  
  
  RESULTS
  In SLE patients, the number of CD200+ cells and the level of soluble CD200 were significantly higher than in healthy controls, whereas the expression of CD200R1 by CD4+ T cells and DCs was decreased. Furthermore, the increased CD200 expression by early apoptotic cells contributed to their diminished binding and phagocytosis by DCs in SLE. Importantly, the engagement of CD200 receptor on CD4+ T cells with CD200-Fc fusion protein in vitro reduced the differentiation of T-helper type 17 cells and reversed the defective induction of CD4+CD25highFoxP3+ T cells by transforming growth factor beta in SLE patients. Conversely, blockade of CD200-CD200R1 interaction with anti-CD200R1 antibody promoted CD4+ T-cell proliferation.
  
  
  CONCLUSIONS
  CD200 and CD200R1 expression and function are abnormal in SLE and may contribute to the immunologic abnormalities in SLE.
authors.affiliation: Department of Rheumatology & Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 41# Da-Mu-Cang-Hu-Tong Street, Beijing 100032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Li-dan
authors.initials: LD
authors.lastname: Zhao
authors.forename: Lu-sha
authors.initials: LS
authors.lastname: Tong
authors.forename: Su-ning
authors.initials: SN
authors.lastname: Qian
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Ding
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: Yan-xia
authors.initials: YX
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiao-feng
authors.initials: XF
authors.lastname: Zeng
authors.forename: Feng-chun
authors.initials: FC
authors.lastname: Zhang
authors.forename: Fu-lin
authors.initials: FL
authors.lastname: Tang
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: De-nian
authors.initials: DN
authors.lastname: Ba
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Xue-tao
authors.initials: XT
authors.lastname: Cao
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D000954:Antigens, Surface / Q000096:biosynthesis / Q000276:immunology*; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002648:Child; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D064446:Orexin Receptors; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000276:immunology*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; C477337:CD200R1 protein, human; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; C042739:antigens, CD200