Aberrant CD200-CD200R1 expression and function in systemic lupus erythematosus contributes to abnormal T-cell responsiveness and dendritic cell activity Reportar como inadecuado

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Arthritis Research and Therapy

, 14:R123

First Online: 23 May 2012Received: 17 February 2012Revised: 17 April 2012Accepted: 23 May 2012


IntroductionCD200 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.

MethodsSerum 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.

ResultsIn 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 CD4CD25FoxP3 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.

ConclusionCD200 and CD200R1 expression and function are abnormal in SLE and may contribute to the immunologic abnormalities in SLE.

AbbreviationsCD200R1CD200 receptor 1

DCdendritic cell

DOK2downstream of tyrosine kinase 2

dsDNAdouble-stranded DNA

ELISAenzyme-linked immunosorbent assay

FCSfetal calf serum

GM-CSFgranulocyte-macrophage colony-stimulating factor

HChealthy control



mAbmonoclonal antibody

PBMCperipheral blood mononuclear cells

PBSphosphate-buffered saline

PIpropidium iodide

RANTESregulated on activation, normal T-cell expressed and secreted

SLEsystemic lupus erythematosus

TGF-βtransforming growth factor beta

Th17T-helper type 17

TNFtumor necrosis factor

Tregregulatory T cell.

Electronic supplementary materialThe online version of this article doi:10.1186-ar3853 contains supplementary material, which is available to authorized users.

Yang Li, Li-dan Zhao, Lu-sha Tong contributed equally to this work.

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Autor: Yang Li - Li-dan Zhao - Lu-sha Tong - Su-ning Qian - Yan Ren - Lei Zhang - Xin Ding - Yang Chen - Yan-xia Wang - Wen Zha

Fuente: https://link.springer.com/

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