ArticlePloS one2013
Intestinal intraepithelial lymphocyte-enterocyte crosstalk regulates production of bactericidal angiogenin 4 by Paneth cells upon microbial challenge.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
40 citing papers in PubMed, 61 citations in OpenAlex.
- Crosstalk between the microbiota and intestinal γδ T cell compartments in health and IBD.Gut microbes · 2026Review
- The Role of Gut Microbiota in Modulating Immune Signaling Pathways in Autoimmune Diseases.Neuromolecular medicine · 2025Review
- Ligands for Intestinal Intraepithelial T Lymphocytes in Health and Disease.Pathogens (Basel, Switzerland) · 2025Review
- Article
- Ribonucleases of Mice and Men: Unveiling the Roles of the RNase A Superfamily in Host Defence.Journal of immunology research · 2025Review
- Crohn's disease: Why the ileum?World journal of gastroenterology · 2023Review
- Review
- Ang1 and Ang4 differentially affect colitis and carcinogenesis in an AOM-DSS mouse model.PloS one · 2023Article
- Metabolic regulation of γδ intraepithelial lymphocytes.Discovery immunology · 2023Article
- Dual function of angiogenin-4 inducing intestinal stem cells and apoptosis.Frontiers in cell and developmental biology · 2023Article
- Review
- Epithelial HNF4A shapes the intraepithelial lymphocyte compartment via direct regulation of immune signaling molecules.The Journal of experimental medicine · 2022Article
- IL-22 initiates an IL-18-dependent epithelial response circuit to enforce intestinal host defence.Nature communications · 2022Article
- Human and mouse angiogenins: Emerging insights and potential opportunities.Frontiers in microbiology · 2022Review
- Current and future aspects of IBD research and treatment: The 2022 perspective.Frontiers in gastroenterology (Lausanne, Switzerland) · 2022Review
- Identification of Crucial Amino Acid Residues for Antimicrobial Activity of Angiogenin 4 and Its Modulation of Gut Microbiota in Mice.Frontiers in microbiology · 2022Article
- A potent HNF4α agonist reveals that HNF4α controls genes important in inflammatory bowel disease and Paneth cells.PloS one · 2022Article
- Bile Acid Regulates the Colonization and Dissemination ofJournal of fungi (Basel, Switzerland) · 2021Article
- Enterocytes in Food Hypersensitivity Reactions.Animals : an open access journal from MDPI · 2021Article
- Bacterial-Specific Aggregation and Killing of Immunomodulatory Host Defense Peptides.Pharmaceuticals (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Antimicrobial proteins influence intestinal microbial ecology and limit proliferation of pathogens, yet the regulation of their expression has only been partially elucidated. Here, we have identified a putative pathway involving epithelial cells and intestinal intraepithelial lymphocytes (iIELs) that leads to antimicrobial protein (AMP) production by Paneth cells. Mice lacking γδ iIELs (TCRδ(-/-)) express significantly reduced levels of the AMP angiogenin 4 (Ang4). These mice were also unable to up-regulate Ang4 production following oral challenge by Salmonella, leading to higher levels of mucosal invasion compared to their wild type counterparts during the first 2 hours post-challenge. The transfer of γδ iIELs from wild type (WT) mice to TCRδ(-/-) mice restored Ang4 production and Salmonella invasion levels were reduced to those obtained in WT mice. The ability to restore Ang4 production in TCRδ(-/-) mice was shown to be restricted to γδ iIELs expressing Vγ7-encoded TCRs. Using a novel intestinal crypt co-culture system we identified a putative pathway of Ang4 production initiated by exposure to Salmonella, intestinal commensals or microbial antigens that induced intestinal epithelial cells to produce cytokines including IL‑23 in a TLR-mediated manner. Exposure of TCR-Vγ7(+) γδ iIELs to IL-23 promoted IL‑22 production, which triggered Paneth cells to secrete Ang4. These findings identify a novel role for γδ iIELs in mucosal defence through sensing immediate epithelial cell cytokine responses and influencing AMP production. This in turn can contribute to the maintenance of intestinal microbial homeostasis and epithelial barrier function, and limit pathogen invasion.
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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.