IRF4 and its regulators: evolving insights into the pathogenesis of inflammatory arthritis?
Accumulating evidence from murine and human studies supports a key role for interleukin-17 (IL-17) and IL-21 in the pathogenesis of inflammatory arthritis. The pathways and molecular mechanisms that underlie the production of IL-17 and IL-21 are being rapidly elucidated. This review focuses on interferon regulatory factor 4 (IRF4), a member of the IRF family of transcription factors, which has emerged as a crucial controller of both IL-17 and IL-21 production. We first outline the complex role of IRF4 in the function of CD4(+) T cells and then discuss recent studies from our laboratory that have revealed a surprising role for components of Rho GTPase-mediated pathways in controlling the activity of IRF4. A better understanding of these novel pathways will hopefully provide new insights into mechanisms responsible for the development of inflammatory arthritis and potentially guide the design of novel therapeutic approaches.
Biswas
Partha S
PS
Department of Medicine, Columbia University, New York, NY 10032, USA.
Bhagat
Govind
G
Pernis
Alessandra B
AB
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology*; D050835:Interferon Regulatory Factors / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D020741:rho GTP-Binding Proteins / Q000276:immunology; D000098546:Interleukin-21; D000099218:Interferon Regulatory Factor-4
D018836:Inflammation Mediators; D050835:Interferon Regulatory Factors; D020381:Interleukin-17; D007378:Interleukins; D020741:rho GTP-Binding Proteins; D000098546:Interleukin-21; D000099218:Interferon Regulatory Factor-4