The contribution of the innate immune system to inflammatory bowel disease (IBD) is under intensive investigation. While research in animal models has demonstrated that type I interferons (IFN-Is) protect from IBD, studies of patients with IBD have produced conflicting results concerning the therapeutic potential of IFN-Is. Now a team of researchers based in Vienna with a contribution of the LBI-CR have resolved this issue.
They present data suggesting that IFN-Is play dual roles as regulators of intestinal inflammation in a mouse model of IBD, dextran sodium sulfate (DSS)-treated C57BL/6 mice. IFN-Is reduced acute intestinal damage and the abundance of colitis-associated intestinal bacteria caused by treatment with a high dose of DSS. However, they also inhibited the resolution of inflammation after DSS treatment. IFN-Is played an anti-inflammatory role by suppressing IL-1 signaling. Consistently, IL-1 receptor blockade reduced the severity of inflammation in IFN-I receptor-deficient mice and myeloid cell-restricted ablation of the IFN-I receptor was detrimental. The proinflammatory role of IFN-Is during recovery from DSS treatment was caused by IFN-I-dependent cell apoptosis as well as an increase in chemokine production and infiltrating inflammatory monocytes and neutrophils. Dagmar Stoiber of the LBI-CR and co-author on the report pointed out, that the reported findings may be important for guiding treatment strategies in patients, as IFN-Is play opposing roles in specific phases of intestinal injury and inflammation.
The report was published recently in the European Journal of Immunology.