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 (2022). Epithelial GPR35 protects from Citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity. Mucosal immunology, 15(3), pp. 443-458. Nature Publishing Group 10.1038/s41385-022-00494-y
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Endocrinology, Diabetology and Clinical Nutrition |
UniBE Contributor: |
Balmer, Maria Luisa |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1933-0219 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
11 Mar 2022 12:17 |
Last Modified: |
05 Dec 2022 16:14 |
Publisher DOI: |
10.1038/s41385-022-00494-y |
PubMed ID: |
35264769 |
BORIS DOI: |
10.48350/167221 |
URI: |
https://boris.unibe.ch/id/eprint/167221 |
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