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December 5, 2005Proceedings of the National Academy of SciencesOpen Access

Reduced Paneth cell α-defensins in ileal Crohn's disease

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Authors

JWJan WehkampJanssen (United States)NSNita H. SalzmanMedical College of WisconsinEPEdith PorterCalifornia State University Los Angeles

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Overview

Translational study reveals reduced Paneth cell alpha-defensins in ileal Crohn's disease, suggesting impaired mucosal innate immunity contributes to disease pathogenesis.

Key Points

  • To determine whether reduced expression of Paneth cell alpha-defensins impairs mucosal antibacterial defenses and contributes to the pathogenesis of ileal Crohn's disease.
  • Assayed antibacterial activity and quantified expression of Paneth cell alpha-defensins (HD5 and HD6) and eight other Paneth cell products in mucosal extracts from patients with ileal Crohn's disease, colonic Crohn's disease, ulcerative colitis, pouchitis, and controls.
  • Evaluated the impact of human alpha-defensin HD5 expression levels on luminal microbiota composition using a transgenic mouse model.
  • Mucosal extracts from patients with ileal Crohn's disease showed reduced antibacterial activity and a specific decrease in HD5 and HD6 expression, whereas eight other Paneth cell products remained unchanged or increased.
  • The reduction in alpha-defensin expression occurred independently of inflammation severity and was absent in colonic Crohn's disease, ulcerative colitis, and pouchitis.
  • Transgenic mice engineered with altered HD5 expression levels comparable to those in Crohn's disease exhibited significant shifts in luminal microbiota composition.

Cite This Study

Wehkamp et al. (2005) studied this question.

synapsesocial.com/papers/6a6fffc426a7f98052dc8992https://doi.org/10.1073/pnas.0505256102
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