Eukaryotic viruses begin to infect intestinal mucosa early in life, and their richness increases with age. It is estimated that the average person has 8-12 chronic viral infections at any given time. Viruses are widespread in the gastrointestinal tract, despite the absence of symptoms, which may indicate that the intestinal mucosa is characterized by frequent infections that can have beneficial and/or harmful effects. In the early stages of a viral infection, the innate immune system is activated, leading to the rapid release of cytokines and subsequent initiation of downstream responses, including inflammation. In the past, enteric viruses were thought to be either harmful or neutral to the host. However, persistent viruses may have a role as resident commensals and provide protective immunity during inflammation. On the other hand, the dysregulation of the intestinal mucosal immune response to viruses can trigger excessive, pathogenic inflammation. An unfavorable change in the viral composition in the intestine can be related to chronic immune disorders, for example in the pathogenesis of IBD. Relatively little is known about the molecular mechanisms involved in both maintenance and wound repair in the intestinal epithelium, but these mechanisms can be seen in the context of immune responses against viral infections. A dysregulation of the intestinal epithelium's immune response to environmental factors, such as e.g. virus, can trigger an excessive pathological inflammation and an exacerbation of inflammatory bowel diseases. An increased understanding of the role that viruses play in intestinal immunity is fundamental to developing therapeutic strategies. So far in the project, we have published a review article in the International Journal of Molecular Sciences by invitation from the journal, where we discuss virus-induced innate immune responses that play a role in a type of IBD; ulcerative colitis. PMID: 34639191

Interferons (IFN) are produced by, among other things, viral infections. Of the various types of interferon, type III IFNs are believed to behave as better immunomodulators than type I IFNs, in light of their limited action in epithelial cells. Induction of type III IFNs can be thought to be triggered through Interferon Regulatory Factor 1 (IRF1) after activation of the peroxisomal signaling pathway. The IBD research group has previously found that IRF1 is strongly upregulated in epithelial cells in active disease compared to inactive disease. In this project, we characterize the importance of the peroxisome as a signaling platform downstream of immune receptor activation. This unconventional signaling pathway was reported to induce the anti-inflammatory cytokine IL15, which could therefore exert a protective mechanism against an exaggerated immune response in the gut. We are in the process of characterizing the various molecular components involved.