[Involvement of CD40-CD154 interaction in immunopathogenesis of collagen diseases and its application to a novel therapeutic strategy].
CD40 and CD154 belong to the tumor necrosis factor (TNF) receptor superfamily and the TNF superfamily, respectively. Evidence is accumulating that indicates the importance of this receptor-ligand pair in the immunopathogenesis of autoimmune diseases. The CD40-CD154 interaction influences antigen presentation, tolerance, autoantibody production and tissue damage, all of which are relevant to the development and perpetuation of autoimmune diseases. Among the collagen diseases, the CD40-CD154 interaction has been intensively investigated in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In this article, both basic and clinical research suggesting the involvement of the CD40-CD154 interaction in SLE, RA, inflammatory myopathies, systemic sclerosis and antiphospholipid syndrome are reviewed. The results of clinical trials from CD40-CD154 blockade are also analyzed. CD40-CD154 blockade in animal models of autoimmune diseases has been reported to be a promising novel therapeutic approach and, thus, has attracted great attention from pharmaceutical companies. However, the development of CD40-CD154 blockers with both significant clinical efficacy and safety has not been successful and research advances in this field are eagerly awaited.
Harigai
Masayoshi
M
Clinical Research Center, and Department of Medicine and Rheumatology, Tokyo Medical and Dental University.
D000818:Animals; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D003095:Collagen Diseases / Q000276:immunology* / Q000628:therapy; D006801:Humans
D019013:CD40 Antigens; D023201:CD40 Ligand