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 (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

Preview

Text s41385-022-00494-y.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (4MB) | Preview

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.

Interest & Impact

Downloads

53 since deposited on 11 Mar 2022
41 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item