Cells of the synovium in rheumatoid arthritis. Dendritic cells

Abstract

Dendritic cells are the major antigen-presenting and antigenpriming cells of the immune system. We review the antigenpresenting and proinflammatory roles played by dendritic cells in the initiation of rheumatoid arthritis (RA) and atherosclerosis, which complicates RA. Various signals that promote the activation of NF-κB and the secretion of TNF and IL-1 drive the maturation of dendritic cells to prime self-specific responses, and drive the perpetuation of synovial inflammation. These signals may include genetic factors, infection, cigarette smoking, immunostimulatory DNA and oxidized low-density lipoprotein, with major involvement of autoantibodies. We propose that the pathogenesis of RA and atherosclerosis is intimately linked, with the vascular disease of RA driven by similar and simultaneous triggers to NF-κB. IntroductionRheumatoid arthritis (RA) is characterized by systemic and synovial tissue chronic inflammation, and by bone and cartilage erosion and destruction [1]. Autoimmune diseases such as RA result from a process involving three distinct but related components -a break in self-tolerance, development of chronic inflammation in one or several organs, and, if ongoing, tissue destruction and its resultant detrimental effects.Dendritic cells (DC) are essential regulators of both innate and acquired arms of the immune system [2]. Their capacity to prime naïve T lymphocytes for helper and cytotoxic function distinguishes them from other antigen-presenting cells (APC). DC are also essential accessory cells in the generation of primary antibody responses, and are powerful enhancers of natural killer T cells and of natural killer cell cytotoxicity [3]. On the other hand, DC are also involved in the maintenance of tolerance to antigens. Along with the medullary thymic epithelial cells, DC contribute to thymic central tolerance and shaping of the T-cell repertoire by presenting endogenous self-antigens to T cells and deleting those T cells that exhibit strong autoreactivity [4]. In the periphery, resting DC delete autoreactive lymphocytes and expand the population of regulatory T cells. DC therefore have potential use in protective and therapeutic strategies for tolerance restoration in autoimmune diseases (for review see [5]). Dendritic cells play several roles in RADC are likely to contribute in several ways to the pathogenesis of RA. First, it is clear from autoimmune models that DC are able to prime MHC-restricted autoimmune responses in lymphoid organs [6][7][8]. Through this process, DC orchestrate the development of the autoantibody and chronic inflammatory pathology on which the clinical features of RA are based. Second, DC infiltrate synovial tissue and synovial fluid and here are able to take up, process and present antigen locally, contributing to disease perpetuation [9,10]. Animal models and histological evidence show that DC drive the generation of ectopic lymphoid tissue in inflammatory environments, probably including the synovium [8,11]. Furthermore DC, along with synoviocytes and macr...

Dendritic Cells in Autoimmune Diseases

“…DCs enter the inflamed synovium through blood vessels and are found to have activated NF-B pathway. Mature myeloid DCs are in perivascular T cell rich areas of synovial tissue and immature DCs are abundant in the synovial lining and sublining layers of synovium [28,49]. Myeloid DCs can enhance inflammation in the synovium by secreting IL-23 that induces Th17 cells.…”

“…These T cells upon stimulation by activated DCs in the presence of TNF-and IL-1 are shown to drive autoantibody production and proinflammatory arthritogenic response [48]. Further, DCs can present altered citrullinated collagens and fibrin to autoreactive T cells ( Table 2) [49]. DCs enter the inflamed synovium through blood vessels and are found to have activated NF-B pathway.…”

Induction of Autoimmune Arthritis after Direct Injection of Bone Marrow Cells from Arthritis-Prone SKG/Jcl Mice into Bone Cavity of Normal Mice

“…1,2) Despite its importance, the etiological genetic and environmental factors of RA are poorly understood. 1,2) Although there are well-known associations between certain genetic polymorphisms and the development of RA, the concordance rate in monozygotic twins is no more than 15-50%.…”

“…1,2) Despite its importance, the etiological genetic and environmental factors of RA are poorly understood. 1,2) Although there are well-known associations between certain genetic polymorphisms and the development of RA, the concordance rate in monozygotic twins is no more than 15-50%. 1,3,4) Moreover, RA is thought to be caused by the interactions of many factors, such as susceptibility genes, stem cell disorders, viral infection, and environment elements.…”

Ginsenoside metabolite compound K exerts anti-inflammatory effect via suppressing T cell activation

“…It has been reported in numerous studies that DCs play important role in the pathogenesis of autoimmune disease such as RA [24][25][26] . The infiltrated DCs migrate from the inflamed synovium to the draining lymph nodes, present arthritogenic peptide to T cells and activate T cells [27,28] . In inflammation conditions, effector T cells such as Th1 and Th17 can be induced by the migration of DCs [29] .…”