Small bowel enteropathy: role of intraepithelial lymphocytes and of cytokines (IL-12, IFN-gamma, TNF) in the induction of epithelial cell death and renewal
- PMID: 9521083
- DOI: 10.1002/(SICI)1521-4141(199802)28:02<730::AID-IMMU730>3.0.CO;2-U
Small bowel enteropathy: role of intraepithelial lymphocytes and of cytokines (IL-12, IFN-gamma, TNF) in the induction of epithelial cell death and renewal
Abstract
The small bowel mucosa contains within its villus epithelium a large number of intraepithelial lymphocytes (IEL) which upon activation are cytotoxic and release large quantities of IFN-gamma and TNF; these activities are increased by in vitro exposure to IL-12. Mice injected with IL-12 develop severe damage of the villus epithelial cells, in form of apoptosis, necrosis and a third distinct form of cell death, characterized ultrastructurally by progressive cell shrinkage. These lesions are accompanied by a compensatory acceleration of the epithelial renewal, a hallmark of epithelial injury. Use of a variety of mutant mice showed that these lesions require the presence of IEL (all populations being involved, thymus-dependent as well as natural killer-T cell IEL) and the release of IFN-gamma. The critical role of IFN-gamma may result in part from its capacity to induce on epithelial cells the expression of target molecules involved in the different cytotoxic pathways used by IEL. However, injection of IFN-gamma into mutant mice lacking IEL showed that IFN-gamma can directly induce villus epithelial damage as well. On the other hand, injection of TNF induces fulminant apoptosis of villus epithelial cells, starting at the top of the villi; however TNF is not required for IL-12-induced enteropathy, which is unmodified in mutant mice lacking TNF. We propose that, when activated by their cognate ligands and/or IL-12 produced by cells in the lamina propria, IEL eliminate infected and senescent epithelial cells through a combination of cytotoxicity and of IFN-gamma and TNF release. This insures the rapid epithelial renewal of the villi, which in turn helps maintain the functional integrity of the barrier.
Similar articles
-
Epithelium derived interleukin 15 regulates intraepithelial lymphocyte Th1 cytokine production, cytotoxicity, and survival in coeliac disease.Gut. 2006 Apr;55(4):469-77. doi: 10.1136/gut.2005.068684. Epub 2005 Aug 16. Gut. 2006. PMID: 16105889 Free PMC article.
-
Defining the roles of perforin, Fas/FasL, and tumour necrosis factor alpha in T cell induced mucosal damage in the mouse intestine.Gut. 2002 Aug;51(2):155-63. doi: 10.1136/gut.51.2.155. Gut. 2002. PMID: 12117872 Free PMC article.
-
Intestinal intraepithelial lymphocytes sustain the epithelial barrier function against Eimeria vermiformis infection.Infect Immun. 2006 Sep;74(9):5292-301. doi: 10.1128/IAI.02024-05. Infect Immun. 2006. PMID: 16926423 Free PMC article.
-
Monoclonal antibodies to the common gamma-chain as cytokine receptor antagonists in vivo: effect on intrathymic and intestinal intraepithelial T lymphocyte development.J Leukoc Biol. 1998 Jun;63(6):643-9. doi: 10.1002/jlb.63.6.643. J Leukoc Biol. 1998. PMID: 9620654 Review.
-
Cell death in the colonic epithelium during inflammatory bowel diseases: CD95/Fas and beyond.Inflamm Bowel Dis. 2010 Jun;16(6):1071-6. doi: 10.1002/ibd.21191. Inflamm Bowel Dis. 2010. PMID: 20049945 Review.
Cited by
-
Effects of dietary supplementation with purple garlic powder and oregano essential oil on intestinal health in post-weaning piglets from commercial farms.Vet Res Commun. 2023 Jun;47(2):901-909. doi: 10.1007/s11259-022-10053-2. Epub 2022 Dec 15. Vet Res Commun. 2023. PMID: 36520356 Free PMC article.
-
Microencapsulated probiotic Lactiplantibacillus plantarum and/or Pediococcus acidilactici strains ameliorate diarrhoea in piglets challenged with enterotoxigenic Escherichia coli.Sci Rep. 2022 May 3;12(1):7210. doi: 10.1038/s41598-022-11340-3. Sci Rep. 2022. PMID: 35505092 Free PMC article.
-
The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune Diseases.Int J Mol Sci. 2022 Feb 23;23(5):2449. doi: 10.3390/ijms23052449. Int J Mol Sci. 2022. PMID: 35269591 Free PMC article. Review.
-
Celiac Disease Causes Epithelial Disruption and Regulatory T Cell Recruitment in the Oral Mucosa.Front Immunol. 2021 Feb 25;12:623805. doi: 10.3389/fimmu.2021.623805. eCollection 2021. Front Immunol. 2021. PMID: 33717129 Free PMC article.
-
The impact of l-arginine supplementation on the enteral phase of experimental Trichinella spiralis infection in treated and untreated mice.J Parasit Dis. 2020 Dec;44(4):737-747. doi: 10.1007/s12639-020-01245-1. Epub 2020 Jul 25. J Parasit Dis. 2020. PMID: 33184541 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases