Irf5-/- Mice are Protected from Helicobacter hepaticus + Anti IL10 Receptor mAb-Mediated Intestinal Inflammation

IRF5 was first described as a regulator of the innate antiviral response and cell cycle. More recently, IRF5 has been shown to polarise macrophages to a pro-inflammatory state which control Th1/Th17 responses, as well as act as a biomarker of inflammatory macrophages in the inflamed mouse knee. Gain of function IRF5 mutations predisposes patients to autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease (IBD). IBD is a debilitating condition of the gastro-intestinal tract, where patients present with neutrophilia and Th1/Th17 responses.  Here we show a fundamental role for IRF5 in the development of intestinal inflammation in an IL23-driven model of colitis. Irf5^-/- mice infected with Helicobacter hepaticus in the absence of IL10 receptor signalling developed a strongly reduced colitis phenotype compared to wild-type controls, evidenced by lower histopathology and reduced  infiltration of leukocytes. Therefore we conclude that IRF5 may present an attractive target for modulation of IBD.