Show simple item record

dc.contributor.authorGrey, Michael J.
dc.contributor.authorDe Luca, Heidi
dc.contributor.authorWard, Doyle V.
dc.contributor.authorKreulen, Irini A. M.
dc.contributor.authorFoley, Sage E
dc.contributor.authorThiagarajah, Jay R.
dc.contributor.authorMcCormick, Beth A.
dc.contributor.authorTurner, Jerrold R.
dc.contributor.authorLencer, Wayne I.
dc.date2022-08-11T08:08:28.000
dc.date.accessioned2022-08-23T15:55:59Z
dc.date.available2022-08-23T15:55:59Z
dc.date.issued2021-07-28
dc.date.submitted2021-08-26
dc.identifier.citation<p>bioRxiv 2021.07.28.453864; doi: https://doi.org/10.1101/2021.07.28.453864. <a href="https://doi.org/10.1101/2021.07.28.453864" target="_blank" title="view preprint in bioRxiv">Link to preprint on bioRxiv.</a></p>
dc.identifier.doi10.1101/2021.07.28.453864
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29874
dc.description<p>This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.</p>
dc.description.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.
dc.language.isoen_US
dc.relationNow published in The Journal of Clinical Investigation, doi:https://doi.org/10.1172/jci153519
dc.rightsThe 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.
dc.rights.urihttp://creativecommons.org/licenses/by-nd/4.0/
dc.subjectCell Biology
dc.subjectendoplasmic reticulum stress sensor IRE1α
dc.subjectmicrobiota
dc.subjectgut microbes
dc.subjectepithelium
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectDevelopmental Biology
dc.titleThe epithelial-specific ER stress sensor IRE1β enables host-microbiota crosstalk to affect colon goblet cell development [preprint]
dc.typePreprint
dc.source.journaltitlebioRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3099&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/2080
dc.identifier.contextkey24508835
refterms.dateFOA2022-08-23T15:55:59Z
html.description.abstract<p>Epithelial cells lining mucosal surfaces of the gastrointestinal and respiratory tracts uniquely express IRE1β (<em>Ern2</em>), 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 <em>Ern2</em><sup>-/-</sup> 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 <em>Xbp1</em> mRNA to expand ER function and prevent ER stress in goblet cells. Although IRE1α can also splice <em>Xbp1</em> 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.</p>
dc.identifier.submissionpathfaculty_pubs/2080
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.contributor.departmentProgram in Microbiome Dynamics
dc.contributor.departmentMicrobiology and Physiological Systems
dc.contributor.studentSage E Foley
dc.description.thesisprogramImmunology and Microbiology


Files in this item

Thumbnail
Name:
2021.07.28.453864v1.full.pdf
Size:
9.020Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

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.
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.