Review Article | Published:

Immunopathogenesis of IBD: current state of the art

Nature Reviews Gastroenterology & Hepatology volume 13, pages 1327 (2016) | Download Citation

Abstract

IBD is a chronic inflammatory condition of the gastrointestinal tract encompassing two main clinical entities: Crohn's disease and ulcerative colitis. Although Crohn's disease and ulcerative colitis have historically been studied together because they share common features (such as symptoms, structural damage and therapy), it is now clear that they represent two distinct pathophysiological entities. Both Crohn's disease and ulcerative colitis are associated with multiple pathogenic factors including environmental changes, an array of susceptibility gene variants, a qualitatively and quantitatively abnormal gut microbiota and a broadly dysregulated immune response. In spite of this realization and the identification of seemingly pertinent environmental, genetic, microbial and immune factors, a full understanding of IBD pathogenesis is still out of reach and, consequently, treatment is far from optimal. An important reason for this unsatisfactory situation is the currently limited comprehension of what are the truly relevant components of IBD immunopathogenesis. This article will comprehensively review current knowledge of the classic immune components and will expand the concept of IBD immunopathogenesis to include various cells, mediators and pathways that have not been traditionally associated with disease mechanisms, but that profoundly affect the overall intestinal inflammatory process.

Key points

  • Substantial progress has been made in the understanding of IBD immunopathogenesis during the past few decades

  • Discovery of the cellular and molecular mediators of intestinal inflammation has led to the development of new therapies that clearly have benefited patients with IBD

  • Environmental, genetic and microbial factors interact with the immune system, resulting in dysregulated immune responses responsible for chronic intestinal inflammation typical of Crohn's disease and ulcerative colitis

  • IBD pathogenesis also includes the effects of other cells involved in the inflammatory processes (such as epithelial, endothelial, mesenchymal and fat cells), as well as other components (such as the inflammasome and regulatory RNAs)

  • Immunopathogenic events are only one component of IBD and they must be interpreted in the context of the other components; that is, the environment, genome and microbiota

  • Only the functional integration of all the underlying components will lead to a full understanding and cure of IBD

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Author information

Affiliations

  1. Department of Gastroenterology & Multidisciplinary Research Laboratory, Federal University of Rio de Janeiro, Rio de Janeiro 21941–913, Brazil.

    • Heitor S. P. de Souza
  2. Department of Pathobiology, Lerner Research Institute, Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.

    • Claudio Fiocchi

Authors

  1. Search for Heitor S. P. de Souza in:

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Contributions

Both authors contributed equally to all aspects of this manuscript.

Competing interests

H.S.P.d.S. and C.F. declare no competing interests.

Corresponding author

Correspondence to Claudio Fiocchi.

Supplementary information

Word documents

  1. 1.

    Supplementary Table 1

    Genetic polymorphisms associated with Crohn's disease and implications for pathogenic mechanisms

  2. 2.

    Supplementary Table 2

    Genetic polymorphisms associated with ulcerative colitis and implications for pathogenic mechanisms

  3. 3.

    Supplementary Table 3

    Genetic polymorphisms associated with both Crohn's disease and ulcerative colitis and implications for pathogenic mechanisms

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https://doi.org/10.1038/nrgastro.2015.186

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