Role of Macrophages in Inflammation Determined by Interferon Regulatory Factor

This gene encodes a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. In particular, the investigators were interested in the effect of IRF5 on proinflammatory M1 macrophages.

The study was carried out using M1 and M2 (noninflammatory) macrophage cultures. The investigators employed a viral vector to infect the cultures with the IRF5 gene, which resulted in overexpression of IRF5 protein.

They reported in the January 16, 2011, online edition of the journal Nature Immunology that overexpression of IRF5 caused M2 noninflammatory macrophages to convert to the M1 phenotype and promote inflammation. In contrast, chemical blocking of IRF5 activity in M1 proinflammatory macrophages reduced the cells' production of interleukins that promote inflammation. Reduced proinflammatory interleukin production was also seen in a population of mice that had been genetically engineered to lack the IRF5 gene.

Senior author Dr. Irina, professor of rheumatology at Imperial College London, said, "Diseases can affect which genes are switched on and off in particular types of cells. Understanding how this switching is regulated is crucial for designing targeted strategies to suppress unwanted cell responses. Our results show that IRF5 is the master switch in a key set of immune cells, which determines the profile of genes that get turned on in those cells. This is really exciting because it means that if we can design molecules that interfere with IRF5 function, it could give us new anti-inflammatory treatments for a wide variety of conditions.”

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