Cargando…
Epithelial GPR35 protects from Citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity
Goblet cells secrete mucin to create a protective mucus layer against invasive bacterial infection and are therefore essential for maintaining intestinal health. However, the molecular pathways that regulate goblet cell function remain largely unknown. Although GPR35 is highly expressed in colonic e...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9038528/ https://www.ncbi.nlm.nih.gov/pubmed/35264769 http://dx.doi.org/10.1038/s41385-022-00494-y |
_version_ | 1784693943044145152 |
---|---|
author | Melhem, Hassan Kaya, Berna Kaymak, Tanay Wuggenig, Philipp Flint, Emilio Roux, Julien Oost, Koen C. Cavelti-Weder, Claudia Balmer, Maria L. Walser, Jean-Claude Morales, Rodrigo A. Riedel, Christian U. Liberali, Prisca Villablanca, Eduardo J. Niess, Jan Hendrik |
author_facet | Melhem, Hassan Kaya, Berna Kaymak, Tanay Wuggenig, Philipp Flint, Emilio Roux, Julien Oost, Koen C. Cavelti-Weder, Claudia Balmer, Maria L. Walser, Jean-Claude Morales, Rodrigo A. Riedel, Christian U. Liberali, Prisca Villablanca, Eduardo J. Niess, Jan Hendrik |
author_sort | Melhem, Hassan |
collection | PubMed |
description | Goblet cells secrete mucin to create a protective mucus layer against invasive bacterial infection and are therefore essential for maintaining intestinal health. However, the molecular pathways that regulate goblet cell function remain largely unknown. Although GPR35 is highly expressed in colonic epithelial cells, its importance in promoting the epithelial barrier is unclear. In this study, we show that epithelial Gpr35 plays a critical role in goblet cell function. In mice, cell-type-specific deletion of Gpr35 in epithelial cells but not in macrophages results in goblet cell depletion and dysbiosis, rendering these animals more susceptible to Citrobacter rodentium infection. Mechanistically, scRNA-seq analysis indicates that signaling of epithelial Gpr35 is essential to maintain normal pyroptosis levels in goblet cells. Our work shows that the epithelial presence of Gpr35 is a critical element for the function of goblet cell-mediated symbiosis between host and microbiota. |
format | Online Article Text |
id | pubmed-9038528 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-90385282022-04-29 Epithelial GPR35 protects from Citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity Melhem, Hassan Kaya, Berna Kaymak, Tanay Wuggenig, Philipp Flint, Emilio Roux, Julien Oost, Koen C. Cavelti-Weder, Claudia Balmer, Maria L. Walser, Jean-Claude Morales, Rodrigo A. Riedel, Christian U. Liberali, Prisca Villablanca, Eduardo J. Niess, Jan Hendrik Mucosal Immunol Article Goblet cells secrete mucin to create a protective mucus layer against invasive bacterial infection and are therefore essential for maintaining intestinal health. However, the molecular pathways that regulate goblet cell function remain largely unknown. Although GPR35 is highly expressed in colonic epithelial cells, its importance in promoting the epithelial barrier is unclear. In this study, we show that epithelial Gpr35 plays a critical role in goblet cell function. In mice, cell-type-specific deletion of Gpr35 in epithelial cells but not in macrophages results in goblet cell depletion and dysbiosis, rendering these animals more susceptible to Citrobacter rodentium infection. Mechanistically, scRNA-seq analysis indicates that signaling of epithelial Gpr35 is essential to maintain normal pyroptosis levels in goblet cells. Our work shows that the epithelial presence of Gpr35 is a critical element for the function of goblet cell-mediated symbiosis between host and microbiota. Nature Publishing Group US 2022-03-09 2022 /pmc/articles/PMC9038528/ /pubmed/35264769 http://dx.doi.org/10.1038/s41385-022-00494-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Melhem, Hassan Kaya, Berna Kaymak, Tanay Wuggenig, Philipp Flint, Emilio Roux, Julien Oost, Koen C. Cavelti-Weder, Claudia Balmer, Maria L. Walser, Jean-Claude Morales, Rodrigo A. Riedel, Christian U. Liberali, Prisca Villablanca, Eduardo J. Niess, Jan Hendrik Epithelial GPR35 protects from Citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity |
title | Epithelial GPR35 protects from Citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity |
title_full | Epithelial GPR35 protects from Citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity |
title_fullStr | Epithelial GPR35 protects from Citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity |
title_full_unstemmed | Epithelial GPR35 protects from Citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity |
title_short | Epithelial GPR35 protects from Citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity |
title_sort | epithelial gpr35 protects from citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9038528/ https://www.ncbi.nlm.nih.gov/pubmed/35264769 http://dx.doi.org/10.1038/s41385-022-00494-y |
work_keys_str_mv | AT melhemhassan epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity AT kayaberna epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity AT kaymaktanay epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity AT wuggenigphilipp epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity AT flintemilio epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity AT rouxjulien epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity AT oostkoenc epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity AT caveltiwederclaudia epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity AT balmermarial epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity AT walserjeanclaude epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity AT moralesrodrigoa epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity AT riedelchristianu epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity AT liberaliprisca epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity AT villablancaeduardoj epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity AT niessjanhendrik epithelialgpr35protectsfromcitrobacterrodentiuminfectionbypreservinggobletcellsandmucosalbarrierintegrity |