Cell and cytokine imbalances in rheumatoid synovitis.
Rheumatoid synovitis is a complex process in which systemic and local homeostatic dysregulation is expressed in the joint. The main genetic susceptibility factors are HLA-DRB1 alleles containing the shared epitope. Environmental factors predominate over genetic factors in the pathogenesis of rheumatoid arthritis (RA), and among them smoking is the most powerful. In RA, disruptions in self-tolerance lead to abnormalities such as recognition of citrullinated antigens by B and T cells. The balance of lymphocyte differentiation in RA is skewed toward the Th1 phenotype, to the detriment of the Th2, Th17, and T regulator (Treg) phenotypes. Imbalances occur in the main cytokine systems including IL-1, TNF, IL-6, IL-18, IL-15, IL-33, IL-22, and IL-13. The joint destruction seen in RA is caused not only by these cytokine imbalances, but also by specific effects of the Wnt system and osteoprotegerin on osteoclasts and by matrix production dysregulation responsible for cartilage damage.
Boissier
Marie-Christophe
MC
EA4222, Service de Rhumatologie, CHU Avicenne, AP-HP, Université Paris-13, PRES Sorbonne-Paris-Cité, 93000 Bobigny, France. boissier@univ-paris13.fr
D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D015551:Autoimmunity / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D007596:Joints / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors; D017634:Self Tolerance / Q000276:immunology; D012907:Smoking / Q000009:adverse effects; D013585:Synovitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains