AUTHOR=King Mikayla R. , Kemp Roslyn A. , Gadeock Safina 

TITLE=Type I interferons in inflammatory bowel diseases: balancing barrier integrity, repair and inflammation in the intestinal epithelium

JOURNAL=Frontiers in Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1713424

DOI=10.3389/fmed.2025.1713424

ISSN=2296-858X

ABSTRACT=Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are persistent, relapsing immune mediated disorders of the gastrointestinal tract associated with significant morbidity and considerable health-care costs. Current therapeutic strategies, such as corticosteroids, immunomodulators, and biologic agents including anti-tumour necrosis factor (anti-TNF) therapies, provide a clinical advantage; however, there is a 30–40% primary non-response rate followed by a 50% secondary non-response rate. This highlights the need for novel therapeutic targets that can specifically address patient heterogeneity. Type I interferons (IFN-Is) are broad acting cytokines that apply state-dependent effects on epithelial intestinal homeostasis. At normal biological levels, IFN-Is reinforce epithelial barrier integrity by regulating tight junction formation, epithelial turnover, and antiviral defence mechanisms. However, in IBD, dysregulated IFN-I signalling facilitates atypical immune cell recruitment, epithelial apoptosis, and prolonged epithelial cell inflammation. The impact of IFN-Is on the dysregulation of the epithelial barrier in IBD remains poorly understood. Patient-derived intestinal organoids represent a physiologically relevant model that aids in the understanding of IFN-I signalling pathways in epithelial cells, allowing for adequate studies on the epithelial–immune crosstalk phenomenon in IBD. This review identifies and highlights IFN-Is as a promising but context-dependent therapeutic target. Interpreting the molecular mechanisms of IFN-Is and their role on the intestinal epithelial barrier function will benefit our understanding of treatment responsiveness as well as aid in resolving current therapeutic challenges in IBD.