Cargando…
IFN-γ mediates Paneth cell death via suppression of mTOR
Paneth cells constitutively produce antimicrobial peptides and growth factors that allow for intestinal homeostasis, host protection, and intestinal stem cell replication. Paneth cells rely heavily on the glycolytic metabolic program, which is in part controlled by the kinase complex Mechanistic tar...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570691/ https://www.ncbi.nlm.nih.gov/pubmed/34633285 http://dx.doi.org/10.7554/eLife.60478 |
_version_ | 1784594880339640320 |
---|---|
author | Araujo, Alessandra Safronova, Alexandra Burger, Elise López-Yglesias, Américo Giri, Shilpi Camanzo, Ellie T Martin, Andrew T Grivennikov, Sergei Yarovinsky, Felix |
author_facet | Araujo, Alessandra Safronova, Alexandra Burger, Elise López-Yglesias, Américo Giri, Shilpi Camanzo, Ellie T Martin, Andrew T Grivennikov, Sergei Yarovinsky, Felix |
author_sort | Araujo, Alessandra |
collection | PubMed |
description | Paneth cells constitutively produce antimicrobial peptides and growth factors that allow for intestinal homeostasis, host protection, and intestinal stem cell replication. Paneth cells rely heavily on the glycolytic metabolic program, which is in part controlled by the kinase complex Mechanistic target of rapamycin (mTORC1). Yet, little is known about mTOR importance in Paneth cell integrity under steady-state and inflammatory conditions. Our results demonstrate that IFN-γ, a crucial mediator of the intestinal inflammation, acts directly on murine Paneth cells to alter their mitochondrial integrity and membrane potential, resulting in an TORC1-dependent cell death mechanism distinct from canonical cell death pathways including apoptosis, necroptosis, and pyroptosis. These results were established with the purified cytokine and a physiologically relevant common Th1-inducing human parasite Toxoplasma gondii. Given the crucial role for IFN-γ, which is a cytokine frequently associated with the development of inflammatory bowel disease and compromised Paneth cell functions, the identified mechanisms underlying mTORC1-dependent Paneth cell death downstream of IFN-γ may provide promising novel approaches for treating intestinal inflammation. |
format | Online Article Text |
id | pubmed-8570691 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-85706912021-11-08 IFN-γ mediates Paneth cell death via suppression of mTOR Araujo, Alessandra Safronova, Alexandra Burger, Elise López-Yglesias, Américo Giri, Shilpi Camanzo, Ellie T Martin, Andrew T Grivennikov, Sergei Yarovinsky, Felix eLife Immunology and Inflammation Paneth cells constitutively produce antimicrobial peptides and growth factors that allow for intestinal homeostasis, host protection, and intestinal stem cell replication. Paneth cells rely heavily on the glycolytic metabolic program, which is in part controlled by the kinase complex Mechanistic target of rapamycin (mTORC1). Yet, little is known about mTOR importance in Paneth cell integrity under steady-state and inflammatory conditions. Our results demonstrate that IFN-γ, a crucial mediator of the intestinal inflammation, acts directly on murine Paneth cells to alter their mitochondrial integrity and membrane potential, resulting in an TORC1-dependent cell death mechanism distinct from canonical cell death pathways including apoptosis, necroptosis, and pyroptosis. These results were established with the purified cytokine and a physiologically relevant common Th1-inducing human parasite Toxoplasma gondii. Given the crucial role for IFN-γ, which is a cytokine frequently associated with the development of inflammatory bowel disease and compromised Paneth cell functions, the identified mechanisms underlying mTORC1-dependent Paneth cell death downstream of IFN-γ may provide promising novel approaches for treating intestinal inflammation. eLife Sciences Publications, Ltd 2021-10-11 /pmc/articles/PMC8570691/ /pubmed/34633285 http://dx.doi.org/10.7554/eLife.60478 Text en © 2021, Araujo et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Araujo, Alessandra Safronova, Alexandra Burger, Elise López-Yglesias, Américo Giri, Shilpi Camanzo, Ellie T Martin, Andrew T Grivennikov, Sergei Yarovinsky, Felix IFN-γ mediates Paneth cell death via suppression of mTOR |
title | IFN-γ mediates Paneth cell death via suppression of mTOR |
title_full | IFN-γ mediates Paneth cell death via suppression of mTOR |
title_fullStr | IFN-γ mediates Paneth cell death via suppression of mTOR |
title_full_unstemmed | IFN-γ mediates Paneth cell death via suppression of mTOR |
title_short | IFN-γ mediates Paneth cell death via suppression of mTOR |
title_sort | ifn-γ mediates paneth cell death via suppression of mtor |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570691/ https://www.ncbi.nlm.nih.gov/pubmed/34633285 http://dx.doi.org/10.7554/eLife.60478 |
work_keys_str_mv | AT araujoalessandra ifngmediatespanethcelldeathviasuppressionofmtor AT safronovaalexandra ifngmediatespanethcelldeathviasuppressionofmtor AT burgerelise ifngmediatespanethcelldeathviasuppressionofmtor AT lopezyglesiasamerico ifngmediatespanethcelldeathviasuppressionofmtor AT girishilpi ifngmediatespanethcelldeathviasuppressionofmtor AT camanzoelliet ifngmediatespanethcelldeathviasuppressionofmtor AT martinandrewt ifngmediatespanethcelldeathviasuppressionofmtor AT grivennikovsergei ifngmediatespanethcelldeathviasuppressionofmtor AT yarovinskyfelix ifngmediatespanethcelldeathviasuppressionofmtor |