The type I IFN system in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder characterized by joint inflammation, immune cell infiltration of the synovia, and cartilage/bone destruction. Despite noteworthy progress in the treatment of RA in recent years, many patients remain refractory to current therapeutic strategies that target either the adaptive immune system or mediators of the innate system. Type I interferons (IFNs) play a significant role in regulation of the innate immune system, originally being discovered as part of intracellular immune defence against viral infection. IFNs are pleiotropic cytokines, mediating both immunostimulatory and immunosuppressive effects. IFN-alpha and beta have been detected in RA synovial fluid and tissue and subsequent therapeutic approaches using type I IFN in murine models of arthritis and in human RA have produced different and controversial results. Great interest has been directed toward principally plasmacytoid dendritic cells (pDCs), although also toward myeloid dendritic cells, as sources of type I IFN. Furthermore, manipulation of DC populations in murine RA models demonstrated that pDCs could suppress the development of arthritis and autoimmunity and may offer an attractive therapy for T-cell-mediated autoimmune diseases. Finally, dendritic cells (DCs) are vehicles for the delivery of therapeutic vaccines, and clinical trials are ongoing in RA with "tolerogenic" DC populations. Further, studies on animal models of RA will elucidate how IFN and DCs contribute to the establishment of autoimmune arthritis and the potential for manipulation of these cell populations and products to re-establish the immune tolerance.
Conigliaro
Paola
P
Division of Rheumatology, Universita' degli studi di Roma Tor Vergata, Rome, Italy.
Perricone
Carlo
C
Benson
Robert A
RA
Garside
Paul
P
Brewer
James M
JM
Perricone
Roberto
R
Valesini
Guido
G
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology*; D051379:Mice
D007370:Interferon Type I