IRF4 and its regulators: evolving insights into the pathogenesis of inflammatory arthritis?
- 23 December 2009
- journal article
- review article
- Published by Wiley in Immunological Reviews
- Vol. 233 (1) , 79-96
- https://doi.org/10.1111/j.0105-2896.2009.00864.x
Abstract
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.Keywords
This publication has 174 references indexed in Scilit:
- Critical Regulation of Early Th17 Cell Differentiation by Interleukin-1 SignalingImmunity, 2009
- Late Developmental Plasticity in the T Helper 17 LineageImmunity, 2008
- IRF-4-Binding Protein Inhibits Interleukin-17 and Interleukin-21 Production by Controlling the Activity of IRF-4 Transcription FactorImmunity, 2008
- Tyrosine-Phosphorylation-Dependent Translocation of the SLAT Protein to the Immunological Synapse Is Required for NFAT Transcription Factor ActivationImmunity, 2008
- Generation of T Follicular Helper Cells Is Mediated by Interleukin-21 but Independent of T Helper 1, 2, or 17 Cell LineagesPublished by Elsevier ,2008
- Molecular Antagonism and Plasticity of Regulatory and Inflammatory T Cell ProgramsPublished by Elsevier ,2008
- The Biological Functions of T Helper 17 Cell Effector Cytokines in InflammationPublished by Elsevier ,2008
- Cytokine Signaling Modules in Inflammatory ResponsesPublished by Elsevier ,2008
- T Helper 17 Lineage Differentiation Is Programmed by Orphan Nuclear Receptors RORα and RORγImmunity, 2008
- GTP‐binding proteins of the Rho/Rac family: regulation, effectors and functions in vivoBioEssays, 2007