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  • Review Article
  • Published:

Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis

Key Points

  • The intestinal microbiota is important for many physiological functions and contributes to host defence by providing resistance to colonization by pathogens and through effects on the mucosal immune system.

  • Paneth cells are specialized secretory epithelial cells that are located in the small intestinal crypts and produce a diverse group of antimicrobial, immune system-stimulating and trophic molecules.

  • Paneth cells have several essential roles for the maintenance of immune homeostasis, such as regulating the composition of the intestinal microbiota, defending against intestinal pathogens and supporting the function of crypt epithelial stem cells.

  • Antimicrobial α-defensins are essential effectors that are produced and secreted by Paneth cells. These effectors modulate acquired immunity in the host through their ability to regulate the composition of the intestinal microbiota.

  • There are numerous susceptibility genes associated with an increased risk of developing Crohn's disease, and many of these genes affect Paneth cell function, strongly suggesting a critical role for these cells in the pathogenesis of Crohn's disease.

Abstract

Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host–microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.

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Figure 1: Morphology and histology of Paneth cells (secretory cells of the small intestinal crypts).
Figure 2: Paneth cell α-defensins, the microbiota and mucosal inflammatory tone.
Figure 3: Paneth cell dysfunction may predispose to intestinal inflammation.

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Acknowledgements

The authors acknowledge the valuable discussions and fruitful collaborations with many investigators in the field that have helped shape the opinions expressed in this Review, including M. A. Zasloff, T. Ganz, A. J. Ouellette, E. M. Porter, L. V. Hooper, B. Shen, A. J. Baumler, J. Wehkamp and E. F. Stange. We apologize for the fact that, because of scope and space restrictions, many interesting investigations could not be included. The authors' work was supported in part by the US National Institutes of Health (grants AI57757, AI32738 and AI50843).

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Correspondence to Nita H. Salzman.

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Glossary

Peyer's patches

Peyer's patches are lymphoid follicles that underlie the small intestinal epithelium, being contained within the intestinal mucosa and submucosa, and that appear as elevated nodules along the surface of the intestinal wall.

Isolated lymphoid follicles

Small aggregates that are formed predominantly of B lymphocytes and are contained within the large and small intestinal mucosae.

Colonocytes

Colonic epithelial cells.

Zymogen

An inactive enzyme precursor (or pro-enzyme).

Pro-inflammatory responses

Host immune responses that cause inflammation, with the release of chemokines and cytokines that result in the attraction and activation of host inflammatory cells.

Hypomorphic

Of a gene mutation: causing reduced gene expression.

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Bevins, C., Salzman, N. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol 9, 356–368 (2011). https://doi.org/10.1038/nrmicro2546

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