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Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI 48109
Systemic lupus erythematosus (SLE) is characterized by a systemic autoimmune response with profound and diverse T cell changes. Dendritic cells (DCs) are important orchestrators of immune responses and have an important role in the regulation of T cell function. The objective of this study was to determine whether myeloid DCs from individuals with SLE display abnormalities in phenotype and promote abnormal T cell function. Monocyte-derived DCs and freshly isolated peripheral blood myeloid DCs from lupus patients displayed an abnormal phenotype characterized by accelerated differentiation, maturation, and secretion of proinflammatory cytokines. These abnormalities were characterized by higher expression of the DC differentiation marker CD1a, the maturation markers CD86, CD80, and HLA-DR, and the proinflammatory cytokine IL-8. In addition, SLE patients displayed selective down-regulation of the maturation marker CD83 and had abnormal responses to maturation stimuli. These abnormalities have functional relevance, as SLE DCs were able to significantly increase proliferation and activation of allogeneic T cells when compared with control DCs. We conclude that myeloid DCs from SLE patients display significant changes in phenotype which promote aberrant T cell function and could contribute to the pathogenesis of SLE and organ damage.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Public Health Service Grants AR050554 and AR048235 and by the Anthony S. Gramer Fund in Inflammation Research (all to M.J.K.). D.D. was supported by Training Grant T32 AR 07080. W.J.M. was supported by the Herb and Carol Amster Lupus Research Fund and the Klein Lupus Research Fund. This research was also supported (in part) by the National Institutes of Health through University of Michigan’s Cancer Center Support Grant (P30 CA46592) and the Rheumatic Diseases Core Center Grant (P30 AR48310).
2 Address correspondence and reprint requests to Dr. Mariana J. Kaplan, Division of Rheumatology, University of Michigan, 5520 MSRBI, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0680. E-mail address: makaplan{at}umich.edu
3 Abbreviations used in this paper: SLE, systemic lupus erythematosus; DC, dendritic cell; RA, rheumatoid arthritis; SLEDAI, SLE disease activity index; 6-MP, 6-mercaptopurine; MMF, mycophenolate-mofetil.
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