ArticleProceedings of the National Academy of Sciences of the United States of America2015
IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 331 papers.
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Who cites it
331 citing papers in PubMed, 508 citations in OpenAlex.
- IL-33 as a boundary-tissue state-transfer signal: a Reader-Alarmin-Effector architecture linking CNS and skin.Brain, behavior, & immunity - health · 2026Review
- Peyer's patch M cells organize an epithelial niche that sustains group 3 innate lymphoid cells and IL-22.Nature immunology · 2026Article
- The Serine Protease-Serine Protease Inhibitor Regulatory Network in Inflammatory Bowel Disease: From Molecular Mechanisms to Novel Therapeutic Horizons.Journal of advanced research · 2026Review
- Interpreting Biomarker Discordance in Inflammatory Bowel Disease: Beyond Fecal Calprotectin and C-Reactive Protein.Biomedicines · 2026Review
- Epithelial-immune interface in asthma: Mechanistic insights driving novel therapeutic strategies.Seminars in immunopathology · 2026Review
- Review
- Recent advances in the pathophysiology of acute and chronic graft-versus-host disease.International journal of hematology · 2026Review
- The Epidermal Growth Factor Receptor (EGFR) as a means of neuro-immune cross-conversation.Journal of neuroinflammation · 2026Review
- ILC2s and their immune checkpoints in the antitumor response.Journal for immunotherapy of cancer · 2026Review
- Review
- Trained ILC2 prevent IL-17-associated lung injury during helminth infection through a serotonin-dependent mechanism.Mucosal immunology · 2026Article
- GPX4-dependent ferroptosis governs ILC2 homeostasis and colitis progression.Cellular & molecular immunology · 2026Article
- Disturbed LTB4 Metabolism in ILC2s Aggravates Ulcerative Colitis via Intercellular ATP Accumulation.Inflammation · 2026Article
- Distinguishing Features of ILC2s During Type 2 Immune Responses.European journal of immunology · 2026Review
- Restoring balance in atopic disorders: insights into type 2 immunity and chronic inflammation.Frontiers in immunology · 2026Review
- ILC imbalance - a new piece in the gut-kidney axis puzzle.Frontiers in immunology · 2026Review
- Critical role of interleukin-33 in pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease.Frontiers in medicine · 2026Review
- Systemic sclerosis-associated pulmonary arterial hypertension and pulmonary fibrosis: exploring biomarker discriminators with advanced omics in a Caucasian cohort.Frontiers in immunology · 2026Article
- Comprehensive insights into the roles of eosinophils in the mucosal immunity of gastrointestinal tract: defenders, destructors, and modulators.Frontiers in immunology · 2026Review
- ILC plasticity in intestinal immune barrier remodeling: current evidence and therapeutic implications for inflammatory bowel disease.Frontiers in immunology · 2026Review
271 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
The barrier surfaces of the skin, lung, and intestine are constantly exposed to environmental stimuli that can result in inflammation and tissue damage. Interleukin (IL)-33-dependent group 2 innate lymphoid cells (ILC2s) are enriched at barrier surfaces and have been implicated in promoting inflammation; however, the mechanisms underlying the tissue-protective roles of IL-33 or ILC2s at surfaces such as the intestine remain poorly defined. Here we demonstrate that, following activation with IL-33, expression of the growth factor amphiregulin (AREG) is a dominant functional signature of gut-associated ILC2s. In the context of a murine model of intestinal damage and inflammation, the frequency and number of AREG-expressing ILC2s increases following intestinal injury and genetic disruption of the endogenous AREG-epidermal growth factor receptor (EGFR) pathway exacerbated disease. Administration of exogenous AREG limited intestinal inflammation and decreased disease severity in both lymphocyte-sufficient and lymphocyte-deficient mice, revealing a previously unrecognized innate immune mechanism of intestinal tissue protection. Furthermore, treatment with IL-33 or transfer of ILC2s ameliorated intestinal disease severity in an AREG-dependent manner. Collectively, these data reveal a critical feedback loop in which cytokine cues from damaged epithelia activate innate immune cells to express growth factors essential for ILC-dependent restoration of epithelial barrier function and maintenance of tissue homeostasis.
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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.