engleski

CHARACTERIZATION OF DENDRITIC CELLS IN SYNOVIAL FLUID, SYNOVIAL MEMBRANE AND PERIPHERAL BLOOD OF RHEUMATOID ARTHRITIS PATIENTS

Background: Since dendritic cells (DCs) are regarded as the professional antigen presenting cells (APC) of the immune system and the only APC capable of activating naive T cells, they are likely to play a significant role in breaking tolerance of self-reactive lymphocytes and in driving the immunophenotypic response underlying rheumatoid arthritis.Rheumatoid arthritis (RA) is one of the most common immune-mediated inflammatory disease characterized by intra-articular inflammation and synovial hyperplasia that results in progressive degradation of cartilage and bone, and often with systemic complications. There is no consensus neither on the type nor the mechanisms by which DCs are involved in inducing a predominant Th1-type inflammatory response in autoimmune pathogenic mechanism of RA. It is proposed that "functional plasticity" of DCs depends either on a subtype of specialized regulatory DCs involved in the process or on the degree of DC maturation during which expression of CD83 and CD1a markers, adhesion and co-stimulatory molecules, as well as chemokine receptors are changing. Objectives: The aim of this study was to characterize the developmental origin, the maturational and activational state, and also chemotactic abilities of DCs from freshly isolated tissue compartments of acute and chronic RA patients and compare them to osteoarthritic (OA) patients. Methods: Samples of peripheral venous blood, synovial fluid and synovial membrane were obtained from 25 patients with RA at the time of hip or knee replacement or at control examination, and from 10 OA patients as a control group. Mononuclear cell populations were separated and analysed by two- and three-color flow cytometry for the following receptors: CD45, CD3, CD4, CD8, CD56+CD16, HLA-DR, CD1a, adhesion molecule CD11c, costimulatory receptors CD83 and CD86 and chemokine receptors CCR5 and CCR7. Results: 1) Based on CD83 and CD1a expression, the prevalence of immature DCs both in the synovial tissue samples and peripheral blood was detected in all groups of examined patients. However, a highly differentiated subpopulation of DCs that expressed an activated phenotype (CD83+, CD86+, HLA-DR+, CD11c+) are detected in higher percentage in acute RA patients comparing to OA patients that serve as a control. 2) Among acute RA patients, a higher degree of CD83+ DCs with antigen presenting (HLA-DR+) and costimulatory (CD86+) phenotype was observed in synovial membrane comparing to synovial fluid and peripheral blood compartments. 3) In all synovial tissue compartments of acute RA patients, CD83+ DCs are predominantly of CD11c+high CD123(IL-3R)+low phenotype, suggesting their myeloid origin, while in peripheral blood, among mature DCs population there are nearly equal distribution of DCs of myeloid and plasmacytoid origin. 4) The expression pattern of CCR5 and CCR7 receptors could partially explain the prevalence of immature DCs in synovial membrane of RA patients. Conclusion: DCs isolated from different tissue compartments in RA patients showed different immunophenotypical characteristics depending on their maturation state, origin, as well as antigen presenting, co-stimulatory and chemotactic activity. These findings suggest that DCs, in the local inflammed environment of RA synovium, could play an essential role in initial pathogenic events of RA leading to autoantigen presentation to T cells, and thus represent new potential therapeutic targets in future.

dendritic cells; synovial membrane; rheumatoid arthritis

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