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Functional expression of 4-1BB (CD137) in the inflammatory tissue in Crohn's disease

Philippe Maerten1, Karel Geboes, Gert De Hertogh

  • 1Clinical Immunology, University Hospital, Katholieke Universiteit Leuven, Leuven, Belgium.

Clinical Immunology (Orlando, Fla.)
|August 17, 2004
PubMed

Insights

The 4-1BB/4-1BBL pathway is implicated in Crohn's disease (CD) pathogenesis. This interaction promotes T cell activation and cytokine production, contributing to chronic gut inflammation in CD patients.

Area of Science:

  • Immunology
  • Gastroenterology
  • Cell Biology

Background:

  • The 4-1BB ligand (4-1BBL) on antigen-presenting cells (APCs) interacts with 4-1BB on activated T cells, promoting T cell costimulation, cytokine secretion, and proliferation.
  • The role of 4-1BB/4-1BBL interactions in the pathogenesis of inflammatory bowel diseases, specifically Crohn's disease (CD), remains to be fully elucidated.

Purpose of the Study:

  • To investigate the involvement of 4-1BB and its ligand (4-1BBL) in the pathogenesis of Crohn's disease (CD).
  • To assess the expression levels of 4-1BB in intestinal tissues of CD patients and compare them to ulcerative colitis (UC) patients and healthy controls.

Main Methods:

  • Immunohistochemistry was used to detect 4-1BB expression on lamina propria (LP) cells in intestinal tissues.
  • Messenger RNA (mRNA) levels for 4-1BB were quantified in intestinal tissues from CD patients and controls.
  • In vitro experiments assessed the sustained expression of 4-1BB on activated LP T cells and the functional effects of agonistic anti-4-1BB antibody on T cell responses.

Main Results:

  • Elevated 4-1BB expression was observed on LP cells in inflamed and non-inflamed gut tissue from CD patients, with increased mRNA levels in intestinal CD tissue.
  • In contrast, minimal 4-1BB expression was found in inflamed tissue from UC patients and control intestinal tissue.
  • LP T cells from CD patients exhibited sustained 4-1BB expression in vitro, and agonistic anti-4-1BB antibody enhanced interferon-gamma (IFN-γ) production and proliferation.

Conclusions:

  • The 4-1BB/4-1BBL interaction is significantly upregulated in the gut of Crohn's disease patients.
  • These interactions appear to contribute to the persistence of gut inflammation in CD by promoting T cell activation and cytokine production.
  • Targeting the 4-1BB/4-1BBL pathway may represent a potential therapeutic strategy for managing Crohn's disease.

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