An Update Review on the Paneth Cell as Key to Ileal Crohn's Disease

Front Immunol. 2020 Apr 15:11:646. doi: 10.3389/fimmu.2020.00646. eCollection 2020.

Abstract

The Paneth cells reside in the small intestine at the bottom of the crypts of Lieberkühn, intermingled with stem cells, and provide a niche for their neighbors by secreting growth and Wnt-factors as well as different antimicrobial peptides including defensins, lysozyme and others. The most abundant are the human Paneth cell α-defensin 5 and 6 that keep the crypt sterile and control the local microbiome. In ileal Crohn's disease various mechanisms including established genetic risk factors contribute to defects in the production and ordered secretion of these peptides. In addition, life-style risk factors for Crohn's disease like tobacco smoking also impact on Paneth cell function. Taken together, current evidence suggest that defective Paneth cells may play the key role in initiating inflammation in ileal, and maybe ileocecal, Crohn's disease by allowing bacterial attachment and invasion.

Keywords: Crohn's disease; Paneth cell; autophagy; bacterial recognition; endosomal stress; ileum; necroptosis.

Publication types

  • Review

MeSH terms

  • Adult Stem Cells / physiology*
  • Animals
  • Autophagy
  • Crohn Disease / immunology
  • Crohn Disease / pathology*
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Ileal Diseases / immunology
  • Ileal Diseases / pathology*
  • Inflammation / immunology
  • Inflammation / pathology*
  • Necroptosis
  • Paneth Cells / physiology*
  • Stem Cell Niche
  • alpha-Defensins / metabolism*

Substances

  • DEFA5 protein, human
  • DEFA6 protein, human
  • alpha-Defensins