ArticleThe Journal of clinical investigation2024
The IRE1α/XBP1 pathway sustains cytokine responses of group 3 innate lymphoid cells in inflammatory bowel disease.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed.
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- Crohn's Disease: From Immune Dysregulation to Intestinal Damage.Inflammation · 2026Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Canonical pathways and selective mechanisms of autophagy in inflammatory bowel disease.Advanced biotechnology · 2026Review
- Human umbilical cord mesenchymal stem cells alleviate colon epithelial apoptosis in ulcerative colitis by activating inositol-requiring enzyme 1/X-box binding protein 1 signaling.Stem cells translational medicine · 2026Article
- D-allose suppresses colitis associated carcinogenesis by reversing ER stress in macrophages and inhibiting cancer cell proliferation.Frontiers in immunology · 2026Article
- Endoplasmic reticulum stress as a mechanistic link between nutrition and inflammatory bowel disease.Frontiers in nutrition · 2026Review
- XBP1 Knockdown Alleviates Pyroptosis and Promotes Th17/Treg Imbalance in Periodontitis by Inhibiting the IL-17 Signaling Pathway.Inflammation · 2025Article
- Biological and clinical implications of a model of surveillance immunity.The Journal of clinical investigation · 2025Review
- Review
- IRE1α and IRE1β Protect Intestinal Epithelium and Suppress Colorectal Tumorigenesis through Distinct Mechanisms.bioRxiv : the preprint server for biology · 2025Article
- EnterohemorrhagicPathogens (Basel, Switzerland) · 2025Article
- Fundamental and emerging insights into innate and adaptive immunity in inflammatory bowel diseases.Frontiers in immunology · 2025Review
- Interaction between Group 3 Innate Lymphoid Cells, Microbiota, and Intestinal Diseases: Mechanisms and Therapeutic Potential.Journal of innate immunity · 2025Review
- Deciphering the immunocellular regulatory network in inflammatory bowel disease: from susceptibility genes to cellular effectors and toward precision therapies.Frontiers in immunology · 2025Review
- Mucosal Single-Cell Profiling of Crohn's-Like Disease of the Pouch Reveals Unique Pathogenesis and Therapeutic Targets.Gastroenterology · 2024Article
- Essential roles of the unfolded protein response in intestinal physiology.eGastroenterology · 2024Review
- A little ER stress isn't bad: the IRE1α/XBP1 pathway shapes ILC3 functions during intestinal inflammation.The Journal of clinical investigation · 2024Article
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10 authors.
Funding
Abstract
Group 3 innate lymphoid cells (ILC3s) are key players in intestinal homeostasis. ER stress is linked to inflammatory bowel disease (IBD). Here, we used cell culture, mouse models, and human specimens to determine whether ER stress in ILC3s affects IBD pathophysiology. We show that mouse intestinal ILC3s exhibited a 24-hour rhythmic expression pattern of the master ER stress response regulator inositol-requiring kinase 1α/X-box-binding protein 1 (IRE1α/XBP1). Proinflammatory cytokine IL-23 selectively stimulated IRE1α/XBP1 in mouse ILC3s through mitochondrial ROS (mtROS). IRE1α/XBP1 was activated in ILC3s from mice exposed to experimental colitis and in inflamed human IBD specimens. Mice with Ire1α deletion in ILC3s (Ire1αΔRorc) showed reduced expression of the ER stress response and cytokine genes including Il22 in ILC3s and were highly vulnerable to infections and colitis. Administration of IL-22 counteracted their colitis susceptibility. In human ILC3s, IRE1 inhibitors suppressed cytokine production, which was upregulated by an IRE1 activator. Moreover, the frequencies of intestinal XBP1s+ ILC3s in patients with Crohn's disease before administration of ustekinumab, an anti-IL-12/IL-23 antibody, positively correlated with the response to treatment. We demonstrate that a noncanonical mtROS-IRE1α/XBP1 pathway augmented cytokine production by ILC3s and identify XBP1s+ ILC3s as a potential biomarker for predicting the response to anti-IL-23 therapies in IBD.
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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 Socratic graph.