title: IRF4 and its regulators: evolving insights into the pathogenesis of inflammatory arthritis?
abstract: 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.
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: Partha S
authors.initials: PS
authors.lastname: Biswas
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.forename: Alessandra B
authors.initials: AB
authors.lastname: Pernis
mesh_terms: 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
chemical_list: 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