Advances and challenges in targeting IRF5, a key regulator of inflammation

FEBS J. 2019 May;286(9):1624-1637. doi: 10.1111/febs.14654. Epub 2018 Sep 21.

Abstract

Interferon regulatory factor 5 (IRF5) belongs to a family of transcription factors, originally implicated in antiviral responses and interferon production. However, studies conducted in different laboratories over the last decade have placed IRF5 as a central regulator of the inflammatory response. It has become clear that IRF5 contributes to the pathogenesis of many inflammatory and autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease and systemic lupus erythematosus. Given the role of IRF5 in physiology and disease, IRF5 represents a potential therapeutic target. However, despite a significant interest from the pharmaceutical industry, inhibitors that interfere with the IRF5 pathway remain elusive. Here, we review the advances made by various studies in targeting multiple steps of signalling leading to IRF5 activation with their therapeutic potential, and the possible complications of such strategies are discussed.

Keywords: autoimmune diseases; inflammation; interferon regulatory factor 5; therapy; transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / metabolism*
  • DNA / metabolism
  • Dimerization
  • Gene Expression Regulation / drug effects
  • Genetic Therapy
  • Humans
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Interferon Regulatory Factors / antagonists & inhibitors
  • Interferon Regulatory Factors / chemistry
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / physiology*
  • Molecular Targeted Therapy
  • Phosphorylation / drug effects
  • Protein Binding / drug effects
  • Protein Interaction Mapping
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Processing, Post-Translational / drug effects
  • RNA Interference
  • RNA, Small Interfering / pharmacology
  • Signal Transduction / drug effects
  • Toll-Like Receptors / physiology
  • Transcription, Genetic

Substances

  • IRF5 protein, human
  • Interferon Regulatory Factors
  • Protein Kinase Inhibitors
  • RNA, Small Interfering
  • Toll-Like Receptors
  • DNA