IRF5 controls both acute and chronic inflammation.

Abstract

Whereas the importance of macrophages in chronic inflammatory diseases is well recognized, there is an increasing awareness that neutrophils may also play an important role. In addition to the well-documented heterogeneity of macrophage phenotypes and functions, neutrophils also show remarkable phenotypic diversity among tissues. Understanding the molecular pathways that control this heterogeneity should provide abundant scope for the generation of more specific and effective therapeutics. We have shown that the transcription factor IFN regulatory factor 5 (IRF5) polarizes macrophages toward an inflammatory phenotype. IRF5 is also expressed in other myeloid cells, including neutrophils, where it was linked to neutrophil function. In this study we explored the role of IRF5 in models of acute inflammation, including antigen-induced inflammatory arthritis and lung injury, both involving an extensive influx of neutrophils. Mice lacking IRF5 accumulate far fewer neutrophils at the site of inflammation due to the reduced levels of chemokines important for neutrophil recruitment, such as the chemokine (C-X-C motif) ligand 1. Furthermore we found that neutrophils express little IRF5 in the joints and that their migratory properties are not affected by the IRF5 deficiency. These studies extend prior ones suggesting that inhibiting IRF5 might be useful for chronic macrophage-induced inflammation and suggest that IRF5 blockade would ameliorate more acute forms of inflammation, including lung injury.

• Authors: Miriam Weiss, Adam J Byrne, Katrina Blazek, David G Saliba, James E Pease, Dany Perocheau, Marc Feldmann, Irina A Udalova
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 112 Issue 35 Pg. 11001-6 (Sep 01 2015) ISSN: 1091-6490 [Electronic] United States
• PMID: 26283380 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines
• Interferon Regulatory Factors
• Irf5 protein, mouse

Topics

• Acute Disease
• Animals
• Chemokines (physiology)
• Chronic Disease
• Inflammation (pathology, physiopathology)
• Interferon Regulatory Factors (physiology)
• Macrophages (pathology)
• Mice
• Synovial Membrane (pathology)