Paneth cell

Paneth cell
Paneth cells, located at the base of the crypts of the small intestinal mucosa, and displaying bright red cytoplasmic granules. H&E stain.
Details
LocationSmall intestine epithelium
Identifiers
Latincellula panethensis
MeSHD019879
THH3.04.03.0.00017
FMA62897
Anatomical terms of microanatomy

Paneth cells are cells in the small intestine epithelium, alongside goblet cells, enterocytes, and enteroendocrine cells.[1] Some can also be found in the cecum and appendix. They are below the intestinal stem cells in the intestinal glands (also called crypts of Lieberkühn) and the large eosinophilic refractile granules that occupy most of their cytoplasm.

These granules consist of several anti-microbial compounds and other compounds that are known to be important in immunity and host-defense. When exposed to bacteria or bacterial antigens, Paneth cells secrete some of these compounds into the lumen of the intestinal gland, thereby contributing to maintenance of the gastrointestinal barrier.

Paneth cells are named after 19th-century pathologist, Joseph Paneth.

Structure

Paneth cells are found throughout the small intestine and the appendix at the base of the intestinal glands.[2] The Paneth cell increase in numbers towards the end of the small intestine. Like the other epithelial cell lineages in the small intestine, Paneth cells originate at the stem cell region near the bottom of the gland.[3]

However, unlike the other epithelial cell types, Paneth cells migrate downward from the stem cell region and settle just adjacent to it.[3] This close relationship to the stem cell region is thought to suggest that Paneth cells are important in defending the gland stem cells from microbial damage,[3] although their function is not entirely known.[2] Furthermore, among the four aforementioned intestinal cell lineages, the Paneth cells live the longest (18–23 days).

Function

Paneth cells secrete antimicrobial peptides and proteins, which are "key mediators of host-microbe interactions, including homeostatic balance with colonizing microbiota and innate immune protection from enteric pathogens."[4]

Small intestinal crypts house stem cells that serve to constantly replenish epithelial cells that die and are lost from the villi.[4]

Protection of these stem cells is essential for long-term maintenance of the intestinal epithelium, and the location of Paneth cells adjacent to stem cells suggests that they play a critical role in defending epithelial cell renewal.[4]

Sensing microbiota

Paneth cells sense bacteria via MyD88-dependent toll-like receptor (TLR) activation which then triggers antimicrobial action.[5]

Secretions

The principal defense molecules secreted by Paneth cells are alpha-defensins, which are known as cryptdins in mice.[6] These peptides have hydrophobic and positively charged domains that can interact with phospholipids in cell membranes. This structure allows defensins to insert into membranes, where they interact with one another to form pores that disrupt membrane function, leading to cell lysis. Due to the higher concentration of negatively charged phospholipids in bacterial than vertebrate cell membranes, defensins preferentially bind to and disrupt bacterial cells, sparing the cells they are functioning to protect.[7]

Paneth cells are stimulated to secrete defensins when exposed to bacteria (both Gram positive and negative types) or such bacterial products as lipopolysaccharide, muramyl dipeptide and lipid A.

In addition to defensins, Paneth cells secrete lysozyme,[8] tumor necrosis factor-alpha,[8] and phospholipase A2. Lysozyme and phospholipase A2 both have clear antimicrobial activity. This battery of secretory molecules gives Paneth cells a potent arsenal against a broad spectrum of agents, including bacteria, fungi and even some enveloped viruses.

Paneth cells participate in the Wnt signaling pathway, which regulates stem cell proliferation in the intestines. Recently, however, it has been discovered that the regenerative potential of intestinal epithelial cells declines over time as a result of aged Paneth cells secreting the protein Notum, which is an extracellular inhibitor of Wnt signaling.[9] If Notum secretion is inhibited, the regenerative potential of the intestinal epithelium could increase.[9]

See also

References

  1. ↑ Horst Ibelgaufts. "Go to Cells-Talk.com". Copewithcytokines.org. Retrieved 2016-09-17.
  2. 1 2 "Paneth's cell | anatomy". Britannica.com. Retrieved 2016-09-17.
  3. 1 2 3 Christopher Duggan; John B. Watkins; W. Allan Walker (2008). Nutrition in Pediatrics: Basic Science, Clinical Applications. p. 244. ISBN 9781550093612. Retrieved 2016-09-17.
  4. 1 2 3 Clevers, HC (2013). "Paneth cells: maestros of the small intestinal crypts". Annual Review of Physiology. 75: 289–311. doi:10.1146/annurev-physiol-030212-183744. PMID 23398152.
  5. ↑ Vaishnava, S; Behrendt, CL; Ismail, AS; Eckmann, L; Hooper, LV (Dec 30, 2008). "Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface". Proceedings of the National Academy of Sciences of the United States of America. 105 (52): 20858–63. Bibcode:2008PNAS..10520858V. doi:10.1073/pnas.0808723105. PMC 2603261. PMID 19075245.
  6. ↑ Wilson C, Ouellette A, Satchell D, Ayabe T, López-Boado Y, Stratman J, Hultgren S, Matrisian L, Parks W (1999). "Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense". Science. 286 (5437): 113–7. doi:10.1126/science.286.5437.113. PMID 10506557.
  7. ↑ Ayabe T, Satchell D, Wilson C, Parks W, Selsted M, Ouellette A (2000). "Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria". Nat Immunol. 1 (2): 113–8. doi:10.1038/77783. PMID 11248802. S2CID 23204633.
  8. 1 2 Kierszenbaum, Abraham L. (2002). Histology and cell biology : an introduction to pathology. St. Louis [u.a.]: Mosby. p. 434. ISBN 0-323-01639-1.
  9. 1 2 Pentinmikko, Nalle; Iqbal, Sharif; Mana, Miyeko; Andersson, Simon; Cognetta, Armand B.; Suciu, Radu M.; Roper, Jatin; Luopajärvi, Kalle; Markelin, Eino; Gopalakrishnan, Swetha; Smolander, Olli-Pekka (July 2019). "Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium". Nature. 571 (7765): 398–402. doi:10.1038/s41586-019-1383-0. hdl:1721.1/126506. ISSN 1476-4687. PMC 8151802. PMID 31292548. S2CID 195873343.
Bibliography
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