Interferons (IFNs) are a broad class of immune mediators that serve fundamental roles during microbial infections as well as during the development of inflammatory disorders. IFNs are divided in three major families: type I IFNs (mainly represented by IFN-αs and IFN-β); type II IFNs (IFN-γ); and type III IFNs (also known as IFN-λ). Since their discovery 15 years ago, type III IFNs were believed to act only on epithelial cells and to share many downstream functions with type I IFNs. We provided novel insights into the biology of type III IFN that may assume specific relevance in the context of inflammatory bowel diseases (IBDs), which occur when the immune system inappropriately responds to the gut microbiome with an aggressive attack that triggers intestinal inflammation and in turn leads to damage. Our findings show that, in the context of intestinal inflammation, type III IFNs act on neutrophils to limit tissue damage, and that blockading type III IFN signaling in neutrophils enhances inflammation in a mouse model of IBD (Nature Immunology, 2017). Our report further establishes that commensal enteric viruses regulate type III interferon-dependent responses, and that exogenous administration of this group of IFNs suppresses intestinal inflammation. These findings setup the essential framework for developing a novel intervention based on type III IFNs, as a possible therapeutic strategy for IBDs.
Currently by using omics, mouse models and IBD patient samples, we are investigating how type III IFN signaling in immune and non-immune cells contribute to IBD development and their involvement in the development of colitis-associated colorectal cancer.
