The epithelial-specific ER stress sensor IRE1β enables host-microbiota crosstalk to affect colon goblet cell development [preprint]
AuthorsGrey, Michael J.
De Luca, Heidi
Ward, Doyle V.
Kreulen, Irini A. M.
Foley, Sage E.
Thiagarajah, Jay R.
McCormick, Beth A.
Turner, Jerrold R.
Lencer, Wayne I.
UMass Chan AffiliationsGraduate School of Biomedical Sciences
Program in Microbiome Dynamics
Department of Microbiology and Physiological Systems
endoplasmic reticulum stress sensor IRE1α
Cellular and Molecular Physiology
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AbstractEpithelial cells lining mucosal surfaces of the gastrointestinal and respiratory tracts uniquely express IRE1β (Ern2), a paralogue of the most evolutionarily conserved endoplasmic reticulum stress sensor IRE1α. How IRE1β functions at the host-environment interface and why a second IRE1 paralogue evolved remain incompletely understood. Using conventionally raised and germ-free Ern2-/- mice, we found that IRE1β was required for microbiota-induced goblet cell maturation and mucus barrier assembly in the colon. This occurred only after colonization of the alimentary tract with normal gut microflora, which induced IRE1β expression. IRE1β acted by splicing Xbp1 mRNA to expand ER function and prevent ER stress in goblet cells. Although IRE1α can also splice Xbp1 mRNA, it did not act redundantly to IRE1β in this context. By regulating assembly of the colon mucus layer, IRE1β further shaped the composition of the gut microbiota. Mice lacking IRE1β had a dysbiotic microbial community that failed to induce goblet cell development when transferred into germ-free wild type mice. These results show that IRE1β evolved at mucosal surfaces to mediate crosstalk between gut microbes and the colonic epithelium required for normal homeostasis and host defense.
bioRxiv 2021.07.28.453864; doi: https://doi.org/10.1101/2021.07.28.453864. Link to preprint on bioRxiv.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/29874
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Except where otherwise noted, this item's license is described as The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.