IL1R2 Acts as a Negative Regulator of Monocyte Recruitment During Inflammation

IL1-β plays a central role in inflammation but its biological action needs to be tightly controlled. Such negative regulation can be exerted by the decoy receptor IL1R2. However, IL1R2 biology in immune cells remains poorly characterized, in particular in monocytes. Using conditional deficient mice, we show that Il1r2 deficiency in monocytes does not affect their steady-state life cycle but dysregulates their trafficking to inflamed tissues in models of peritonitis and neuro-inflammation. Mechanistically, we found that Il1r2 deficiency in monocytes increases CCL2 secretion in the inflamed peritoneum, thereby amplifying monocyte recruitment from blood. In autoimmune neuro-inflammation, Il1r2 deficiency in monocytes exacerbates disease severity. Our findings suggest that the specific action of IL1R2 in monocytes contributes to a feedback mechanism for fine-tuning the numbers of recruited monocytes during inflammation.