Immunopathogenic Mechanisms of Fibrostenotic and Fistulizing Crohn’s Disease Complications

Crohn’s Disease (CD) is an inflammatory bowel disease characterized by patchy, transmural inflammation that in many cases can last for years. Intestinal fibrosis is a severe complication of CD, most commonly occurring in the ileal and ileocolonic regions with de novo stricture formation and recurring fibrotic lesions in 23-40% of patients within 5 years following diagnosis. Fistulas, both perianal and internal, are another complication and 35–50% of CD patients develop at least one fistula episode over the course of the disease. Persistent inflammation has been linked to progressive fibrosis as well as manifestations of strictures and fistula formation. Clinical and preclinical studies suggest that inflammation is important in initiating and driving intestinal fibrogenesis and fistula development. However, current anti-inflammatory and immunomodulatory treatments are insufficient in preventing fibrosis and at best, are modestly effective in preventing fistula complications. Despite advances in the understanding of transmural inflammation in CD, the immunopathogenic mechanisms linked to the development and progression of fibrotic strictures and fistula formation in CD remain to be elucidated.

This Research Topic aims to understand the basic biology and state of the art of research examining immunopathogenic mechanisms driving fibrostenosis, fistula formation and aberrant wound repair in CD. Concepts include the cellular and molecular interplay between immune and non-immune cells as well as inflammatory and non-inflammatory mechanisms of aberrant tissue remodeling leading to fibrostenosis and fistulizing CD. We welcome the submission of Original Research, Review or Mini-Review articles covering, but not limited to, the following subtopics:

• Innate sensing and counter regulatory mechanisms involved in fibrogenesis, fibrostenosis and fistulizing CD
• Redox dysregulation and ER stress linked to tissue remodeling and intestinal fibrosis
• Induction of cell death pathways linked to intestinal fibrogenesis
• Non-inflammatory mechanisms driving intestinal fibrogenesis and extracellular matrix biology
• Stromal and immune cell crosstalk involved in intestinal fibrogenesis, fibrostenosis, and fistula formation



Dr. Gerald Nabozny and Dr. Iganacio Juncadella are employees of Boehringer Ingelheim Pharmaceuticals Inc, involved in the development of therapies. The other Topic Editors declare no potential competing interests in relation to the Research Topic theme.