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With the prevalence of inflammatory bowel diseases (IBD) continuing to rise in Canada and globally, developing improved therapeutics that successfully treat greater percentages of patients with reduced complications is paramount. A better understanding of pertinent immune pathways in IBD will improve our ability to both successfully dampen inflammation and promote gut healing, beyond just inhibiting specific immune proteins; success of combination therapies supports this approach. Interferons (IFNs) are key cytokines that protect mucosal barrier surfaces, and their roles in regulating gut homeostasis and inflammation differ between the three IFN families (type I, II, and III). Interestingly, the gut microbiota and microbial metabolites impact IFN-signaling, yet how this system is impacted in IBD remains unclear. In this review, we discuss the current knowledge of how gut microbiota directly or indirectly impact IFN levels/responses, and what is known about IFNs differentially regulating gut homeostasis and inflammation in animal models or patients with IBD.Inflammatory bowel diseases (IBD) are serious chronic illnesses of the gut that affect over 300,000 Canadians. The current treatments for IBD do not work in all people and many drugs aim to stop our immune system from overreacting. Learning more about the immune pathways not working properly in IBD could help lead to new therapies. There are multiple types of immune proteins called interferons that help us fight pathogens, but they also directly impact gut health in different ways- both good and bad. This review article covers the latest findings on how the microbes in our gut affect interferons and how this could be altered in IBD. More research is needed to fully know how each type of interferon works in the gut, and whether we can use what we learn to help people living with IBD.

To date, only monoclonal antibodies have been shown to be effective for outpatients with COVID-19. Interferon lambda-1 is a type III interferon involved in innate antiviral responses with activity against respiratory pathogens. We aimed to investigate the safety and efficacy of peginterferon lambda in the treatment of outpatients with mild-to-moderate COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells. ACE2has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in ACE2expression levels could be important for susceptibility to COVID-19 or its outcomes. Here, we report the discovery of a novel, transcriptionally independent truncated isoform of ACE2, which we designate as deltaACE2(dACE2). We demonstrate that dACE2, but not ACE2, is an ISG. In The Cancer Genome Atlas, the expression of dACE2was enriched in squamous tumors of the respiratory, gastrointestinal and urogenital tracts. In vitro, dACE2, which lacks 356 amino-terminal amino acids, was non-functional in binding the SARS-CoV-2 spike protein and as a carboxypeptidase. Our results suggest that the ISG-type induction of dACE2in IFN-high conditions created by treatments, an inflammatory tumor microenvironment or viral co-infections is unlikely to increase the cellular entry of SARS-CoV-2 and promote infection.

With the first reports on coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the scientific community working in the field of type III IFNs (IFN-λ) realized that this class of IFNs could play an important role in this and other emerging viral infections. In this Viewpoint, we present our opinion on the benefits and potential limitations of using IFN-λ to prevent, limit, and treat these dangerous viral infections.