Fibroblast Heterogeneity in Inflammatory Bowel Disease

Int J Mol Sci. 2024 Dec 3;25(23):13008. doi: 10.3390/ijms252313008.

Abstract

Intestinal fibroblasts are pivotal players in maintaining tissue homeostasis and orchestrating responses to injury and inflammation within the gastrointestinal (GI) tract. Fibroblasts contribute significantly to the pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC), by secreting pro-inflammatory cytokines, modulating immune cell activity, and promoting fibrosis. In addition, fibroblasts play crucial roles in tissue repair and regeneration following acute injury or chronic inflammation. The dysregulation of fibroblast functions can lead to fibrotic complications, such as intestinal strictures and obstruction, which are common in advanced stages of IBD. Understanding the complex interplay between fibroblasts and other cell types in the intestine is essential to elucidate the underlying mechanisms of intestinal diseases and identify novel therapeutic targets. Future research aimed at deciphering the heterogeneity of intestinal fibroblasts and their dynamic roles in disease progression holds promise for the development of precision therapies to mitigate fibrosis and inflammation in intestinal disorders.

Keywords: fibroblast heterogeneity; fibroblast–immune interaction; inflammatory bowel disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Fibroblasts* / metabolism
  • Fibroblasts* / pathology
  • Fibrosis
  • Humans
  • Inflammatory Bowel Diseases* / metabolism
  • Inflammatory Bowel Diseases* / pathology

Substances

  • Cytokines

Grants and funding

B.-J.K. was supported by funding from Taiwan (Ministry of Education)-KU Leuven Scholarship Programme. G.D. received the European Crohn’s and Colitis Organisation (ECCO) Grant 2020. G.M.’s lab was supported by European Crohn’s and Colitis Organisation (ECCO) Pioneer award 2023, European Union’s Horizon Europe Research & Innovation programme (FIBROTARGET, 101080523), FWO grants (G0D8317N, G0A7919N, G086721N, G088816N, and S008419N, W001620N), and KU Leuven Internal Funds (C12/15/016 and C14/17/097).