Abstract
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction. Although the primacy of T cell-related events early in the disease continues to be debated, there is strong evidence that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. In addition, T cells are key components of the immune cell infiltrate detected in the joints of RA patients. Initial analysis of the cytokines released into the synovial membrane showed an imbalance, with a predominance of proinflammatory mediators, indicating a deleterious effect of Th1 T cells. There is nonetheless evidence that Th17 cells also play an important role in RA. T cells migrate from the bloodstream to the synovial tissue via their interactions with the endothelial cells that line synovial postcapillary venules. At this stage, selectins, integrins, and chemokines have a central role in blood cell invasion of synovial tissue, and therefore in the intensity of the inflammatory response. In this review, we will focus on the mechanisms involved in T cell attraction to the joint, the proteins involved in their extravasation from blood vessels, and the signaling pathways activated. Knowledge of these processes will lead to a better understanding of the mechanism by which the systemic immune response causes local joint disorders and will help to provide a molecular basis for therapeutic strategies.
Highlights
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction
Encodes the cell surface complex for antigen presentation Encodes a tyrosine phosphatase involved in the immune response Encodes a transcription factor implicated in cytokine and chemokine signaling Encodes a regulator of the TNFα receptor Encodes a peptidylarginine deiminase that catalyzes conversion of arginine to citrullin Encodes a member of the interferon regulatory factor Encodes the low affinity IgG Fc receptor Encodes the high affinity IL2 receptor Encodes a costimulatory molecule that enhances B/T cell interactions Encodes a negative regulator of dendritic cells (DCs)/T cell interaction Encodes a chemokine implicated in lymphocyte homing Encodes a chemokine receptor implicated in Th17 recruitment locus suggests the influence of T cell selection and antigen presentation in the induction of autoreactive immune responses [2,3,4]
Other chemokine receptors found in CCR6+ Th cells are CCR5, CXCR4, and CXCR6, they have not been associated with specific cytokine profiles
Summary
Incorrect resolution of inflammation underlies pathologies of clinical importance, including cancer, atherosclerosis, and rheumatic diseases, and precise understanding of inflammatory responses is a major challenge to medical science. Of these conditions, rheumatoid arthritis (RA) is an enormous economic and social problem, highly prevalent in industrialized countries (0.5–1%, with two- to threefold greater incidence in women), resulting in disability, loss in quality of life, and reduced life expectancy. Rheumatoid arthritis is a systemic autoimmune disease, characterized by non-organ-specific autoantibody production and chronic inflammation of synovial tissues, leading to cartilage and bone destruction. Other organs can become inflamed, and as a consequence, systemic cardiovascular, pulmonary, and skeletal complications frequently appear [1]. The long-established association of RA patients with the human leukocyte antigen (HLA)-DRB1
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