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Immunol Rev. 2010 Jan;233(1):79-96. doi: 10.1111/j.0105-2896.2009.00864.x.

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

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Department of Medicine, Columbia University, New York, NY 10032, USA.


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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