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.
Highlights
Crohn’s disease was originally described and established [1] as a chronic ileal inflammation leading to strictures and resection of the involved segment
Following small bowel transplantation, with 35% of the patients possessing NOD2 polymorphisms, rejection was characterized by decreased expression of Paneth cell antimicrobial peptides in the NOD2 mutant recipients, prior to the onset of inflammation [62]
Its levels were significantly decreased in inflamed mucosa of IBD patients and its deletion in mice was associated with diminished Paneth cell defensins [91]
Summary
Crohn’s disease was originally described and established [1] as a chronic ileal inflammation leading to strictures and resection of the involved segment. One possible explanation may be provided by the Paneth cell which resides predominantly in the small intestine, it may be induced by inflammation as a metaplastic cell in other parts of the intestine, such as in the colon. The history of this cell [7] dates back to 1872 when it was first observed by Schwalbe in Freiburg but described in more detail in 1888 by Josef Paneth in Vienna (who quoted Schwalbe and showed one of his pictures). Paneth cells are Janus-faced: they were given the title “maestros of the crypt” [12] but they may be the culprits in Crohn’s disease, hiding backstage behind the T-cells
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