From Birth to Death: The Hardworking Life of Paneth Cell in the Small Intestine

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Mar 27

PMID 36969191

Authors

Chenbin Cui

Fangke Wang

Yao Zheng

Hongkui Wei

Jian Peng

Affiliations

Soon will be listed here.

Abstract

Paneth cells are a group of unique intestinal epithelial cells, and they play an important role in host-microbiota interactions. At the origin of Paneth cell life, several pathways such as Wnt, Notch, and BMP signaling, affect the differentiation of Paneth cells. After lineage commitment, Paneth cells migrate downward and reside in the base of crypts, and they possess abundant granules in their apical cytoplasm. These granules contain some important substances such as antimicrobial peptides and growth factors. Antimicrobial peptides can regulate the composition of microbiota and defend against mucosal penetration by commensal and pathogenic bacteria to protect the intestinal epithelia. The growth factors derived from Paneth cells contribute to the maintenance of the normal functions of intestinal stem cells. The presence of Paneth cells ensures the sterile environment and clearance of apoptotic cells from crypts to maintain the intestinal homeostasis. At the end of their lives, Paneth cells experience different types of programmed cell death such as apoptosis and necroptosis. During intestinal injury, Paneth cells can acquire stem cell features to restore the intestinal epithelial integrity. In view of the crucial roles of Paneth cells in the intestinal homeostasis, research on Paneth cells has rapidly developed in recent years, and the existing reviews on Paneth cells have mainly focused on their functions of antimicrobial peptide secretion and intestinal stem cell support. This review aims to summarize the approaches to studying Paneth cells and introduce the whole life experience of Paneth cells from birth to death.

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References

Batlle E, Henderson J, Beghtel H, van den Born M, Sancho E, Huls G . Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell. 2002; 111(2):251-63. DOI: 10.1016/s0092-8674(02)01015-2. View

Biswas A, Liu Y, Hao L, Mizoguchi A, Salzman N, Bevins C . Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum. Proc Natl Acad Sci U S A. 2010; 107(33):14739-44. PMC: 2930434. DOI: 10.1073/pnas.1003363107. View

Sheahan B, Theriot C, Cortes J, Dekaney C . Prolonged oral antimicrobial administration prevents doxorubicin-induced loss of active intestinal stem cells. Gut Microbes. 2022; 14(1):2018898. PMC: 8757478. DOI: 10.1080/19490976.2021.2018898. View

Berger J, Gong H, Good M, McElroy S . Dithizone-induced Paneth cell disruption significantly decreases intestinal perfusion in the murine small intestine. J Pediatr Surg. 2019; 54(11):2402-2407. PMC: 6707906. DOI: 10.1016/j.jpedsurg.2019.02.021. View

Park S, Kim M, Brown K, DAgati V, Lee H . Paneth cell-derived interleukin-17A causes multiorgan dysfunction after hepatic ischemia and reperfusion injury. Hepatology. 2011; 53(5):1662-75. PMC: 3082595. DOI: 10.1002/hep.24253. View

Hu G, Yang Y, Qin X, Qi S, Zhang J, Yu S . Outer Protein B Suppresses Colitis Development via Protecting Cell From Necroptosis. Front Cell Infect Microbiol. 2019; 9:87. PMC: 6465518. DOI: 10.3389/fcimb.2019.00087. View

de Jong P, Taniguchi K, Harris A, Bertin S, Takahashi N, Duong J . ERK5 signalling rescues intestinal epithelial turnover and tumour cell proliferation upon ERK1/2 abrogation. Nat Commun. 2016; 7:11551. PMC: 4873670. DOI: 10.1038/ncomms11551. View

Clevers H, Bevins C . Paneth cells: maestros of the small intestinal crypts. Annu Rev Physiol. 2013; 75:289-311. DOI: 10.1146/annurev-physiol-030212-183744. View

Cadwell K, Liu J, Brown S, Miyoshi H, Loh J, Lennerz J . A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature. 2008; 456(7219):259-63. PMC: 2695978. DOI: 10.1038/nature07416. View

10.

Annunziata F, Rasa S, Krepelova A, Lu J, Minetti A, Omrani O . Paneth cells drive intestinal stem cell competition and clonality in aging and calorie restriction. Eur J Cell Biol. 2022; 101(4):151282. DOI: 10.1016/j.ejcb.2022.151282. View

11.

Gunther C, Buchen B, He G, Hornef M, Torow N, Neumann H . Caspase-8 controls the gut response to microbial challenges by Tnf-α-dependent and independent pathways. Gut. 2014; 64(4):601-10. PMC: 4392221. DOI: 10.1136/gutjnl-2014-307226. View

12.

Farin H, Jordens I, Mosa M, Basak O, Korving J, Tauriello D . Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. Nature. 2016; 530(7590):340-3. DOI: 10.1038/nature16937. View

13.

Andreu P, Peignon G, Slomianny C, Taketo M, Colnot S, Robine S . A genetic study of the role of the Wnt/beta-catenin signalling in Paneth cell differentiation. Dev Biol. 2008; 324(2):288-96. DOI: 10.1016/j.ydbio.2008.09.027. View

14.

Gunther C, Neumann H, Neurath M, Becker C . Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium. Gut. 2012; 62(7):1062-71. DOI: 10.1136/gutjnl-2011-301364. View

15.

Zhan Y, Xu C, Liu Z, Tan S, Yang Y, Jiang J . β-Arrestin1 inhibits chemotherapy-induced intestinal stem cell apoptosis and mucositis. Cell Death Dis. 2016; 7:e2229. PMC: 4917667. DOI: 10.1038/cddis.2016.136. View

16.

Gaudino S, Beaupre M, Lin X, Joshi P, Rathi S, McLAUGHLIN P . IL-22 receptor signaling in Paneth cells is critical for their maturation, microbiota colonization, Th17-related immune responses, and anti-Salmonella immunity. Mucosal Immunol. 2020; 14(2):389-401. PMC: 7946635. DOI: 10.1038/s41385-020-00348-5. View

17.

Sato T, Vries R, Snippert H, van de Wetering M, Barker N, Stange D . Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009; 459(7244):262-5. DOI: 10.1038/nature07935. View

18.

Wehkamp J, Harder J, Weichenthal M, Schwab M, Schaffeler E, Schlee M . NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut. 2004; 53(11):1658-64. PMC: 1774270. DOI: 10.1136/gut.2003.032805. View

19.

Verdile N, Mirmahmoudi R, Brevini T, Gandolfi F . Evolution of pig intestinal stem cells from birth to weaning. Animal. 2019; 13(12):2830-2839. DOI: 10.1017/S1751731119001319. View

20.

Heuberger J, Kosel F, Qi J, Grossmann K, Rajewsky K, Birchmeier W . Shp2/MAPK signaling controls goblet/paneth cell fate decisions in the intestine. Proc Natl Acad Sci U S A. 2014; 111(9):3472-7. PMC: 3948231. DOI: 10.1073/pnas.1309342111. View