T Cell Migration in Rheumatoid Arthritis.
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.
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones , Madrid , Spain.
Mario
M
Mellado
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones , Madrid , Spain.
Laura
L
Martínez-Muñoz
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones , Madrid , Spain.
Graciela
G
Cascio
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones , Madrid , Spain.
Pilar
P
Lucas
Grupo de Enfermedades Inflamatorias y Autoinmunes, Instituto de Investigación Sanitaria Hospital , Madrid , Spain.
José L
JL
Pablos
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones , Madrid , Spain.
José Miguel
JM
Rodríguez-Frade
cell migration; chemokines; cytokines; inflammation; rheumatoid arthritis