IRF4 and its regulators: evolving insights into the pathogenesis of inflammatory arthritis?

PS Biswas, G Bhagat, AB Pernis - Immunological reviews, 2010 - Wiley Online Library
PS Biswas, G Bhagat, AB Pernis
Immunological reviews, 2010Wiley Online Library
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 …
Summary
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.
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