Iron Regulatory Protein 1 is Required for the Propagation of Inflammation in Inflammatory Bowel Disease

Inflammatory bowel diseases (IBD) are complex disorders characterized by a cycle of inflammatory perpetuation. Iron accumulates in the inflamed tissue of IBD patients, yet neither a mechanism for the accumulation nor its implication on the course of inflammation are known. This study addresses the role of iron homeostasis in IBD using human biopsies, animal models and cellular systems. It demonstrates inflammation-mediated modifications of iron homeostasis, and an iron decoupled activation of the iron regulatory protein (IRP)1. To understand the role of IRP1 in the course of this inflammation-associated iron pattern, a novel cellular co-culture model was established, that reproduced the iron-pattern observed in vivo. Importantly, deletion of IRP1 from an IBD mouse model completely abolished mis-distribution of iron and intestinal inflammation, suggesting a central role of IRP1 in the coordination of inflammatory response in the intestinal mucosa. Thus, this work identifies IRP1 as a target for IBD treatment. ### Competing Interest Statement EGMH and LF are inventors on a Provisional Patent Application, Model for Analyzing inflammation and uses, US Provisional Patent Application No. 633/38,64 related to this work filed jointly by the Technion on July 13, 2022. The remaining authors declare no competing interests.