ArticleThe Journal of clinical investigation2022
The epithelial-specific ER stress sensor ERN2/IRE1β enables host-microbiota crosstalk to affect colon goblet cell development.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- Impacts of trichothecene mycotoxins on human colonic epithelial cells: molecular mechanisms and signaling pathways.Journal of advanced research · 2026Review
- Cell surface GRP78 and the UPR pathway as novel promising therapeutic targets in cancer: an insight into the treatment of acute leukemia by using GRP78-CART cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- The Role of Crosstalk Between the Unfolded Protein Response and Autophagy in Diseases Associated with Sympathetic Nervous System Imbalance: Mechanisms and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- From mucus secretion to immune surveillance: the evolving roles of goblet cells in intestinal homeostasis and inflammation.Frontiers in immunology · 2026Review
- Article
- Mucin 2 and unfolded protein response reshape the mucus barrier in inflammatory bowel disease (Review).Molecular medicine reports · 2026Review
- Endoplasmic reticulum stress as a mechanistic link between nutrition and inflammatory bowel disease.Frontiers in nutrition · 2026Review
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- Development of a Caco-2-based intestinal mucosal model to study intestinal barrier properties and bacteria-mucus interactions.Gut microbes · 2025Article
- High-fat diet, intestinal microecology and bone loss.Nutrition & metabolism · 2025Review
- Endoplasmic Reticulum Stress in Cancer.MedComm · 2025Review
- IRE1α and IRE1β Protect Intestinal Epithelium and Suppress Colorectal Tumorigenesis through Distinct Mechanisms.bioRxiv : the preprint server for biology · 2025Article
- Gut microbiota modulate intestinal inflammation by endoplasmic reticulum stress-autophagy-cell death signaling axis.Journal of animal science and biotechnology · 2025Review
- Endoplasmic reticulum stress in gut inflammation: Implications for ulcerative colitis and Crohn's disease.World journal of gastroenterology · 2025Review
- Review
- KDELR2 is necessary for chronic obstructive pulmonary disease airway Mucin5AC hypersecretion via an IRE1α/XBP-1s-dependent mechanism.Journal of cellular and molecular medicine · 2024Article
- Essential roles of the unfolded protein response in intestinal physiology.eGastroenterology · 2024Review
- Mitochondrial function and gastrointestinal diseases.Nature reviews. Gastroenterology & hepatology · 2024Review
- IRE1α recognizes a structural motif in cholera toxin to activate an unfolded protein response.The Journal of cell biology · 2024Article
- Challenges in IBD Research 2024: Preclinical Human IBD Mechanisms.Inflammatory bowel diseases · 2024Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Epithelial cells lining mucosal surfaces of the gastrointestinal and respiratory tracts uniquely express ERN2/IRE1β, a paralogue of the most evolutionarily conserved endoplasmic reticulum stress sensor, ERN1/IRE1α. How ERN2 functions at the host-environment interface and why a second paralogue evolved remain incompletely understood. Using conventionally raised and germ-free Ern2-/- mice, we found that ERN2 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 Ern2 expression. ERN2 acted by splicing Xbp1 mRNA to expand ER function and prevent ER stress in goblet cells. Although ERN1 can also splice Xbp1 mRNA, it did not act redundantly to ERN2 in this context. By regulating assembly of the colon mucus layer, ERN2 further shaped the composition of the gut microbiota. Mice lacking Ern2 had a dysbiotic microbial community that failed to induce goblet cell development and increased susceptibility to colitis when transferred into germ-free WT mice. These results show that ERN2 evolved at mucosal surfaces to mediate crosstalk between gut microbes and the colonic epithelium required for normal homeostasis and host defense.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.