Interleukin-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability
Open accessAbstract
Whether interleukin-17A (IL-17A) has pathogenic and/or protective roles in the gut mucosa is controversial and few studies have analyzed specific cell populations for protective functions within the inflamed colonic tissue. Here we have provided evidence for IL-17A-dependent regulation of the tight junction protein occludin during epithelial injury that limits excessive permeability and maintains barrier integrity. Analysis of epithelial cells showed that in the absence of signaling via the IL-17 receptor adaptor protein Act-1, the protective effect of IL-17A was abrogated and inflammation was enhanced. We have demonstrated that after acute intestinal injury, IL-23R(+) γδ T cells in the colonic lamina propria were the primary producers of early, gut-protective IL-17A, and this production of IL-17A was IL-23 independent, leaving protective IL-17 intact in the absence of IL-23. These results suggest that IL-17-producing γδ T cells are important for the maintenance and protection of epithelial barriers in the intestinal mucosa.
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From The IL-17 Family of Cytokines in Health and Disease (2019) · cites this paper as Lee et al., 2015
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- Authors
- Lee, J. S., Tato, C. M., Joyce-Shaikh, B., Gulen, M. F., Cayatte, C., Chen, Y., Blumenschein, W. M., Judo, M., Ayanoglu, G., McClanahan, T. K., Li, X., & Cua, D. J.
- Affiliations
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Cleveland Clinic (US)
- Corresponding author
- Cua, Daniel J.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 43
- Issue
- 4
- Pages
- 727-738
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC6044435
- OpenAlex
- W1836263069
- Cited by
- 760
- References
- 50
- Citations by year
- 2026: 59 · 2025: 67 · 2024: 70 · 2023: 77 · 2022: 73 · 2021: 95 · 2020: 72 · 2019: 86 · 2018: 75 · 2017: 47 · 2016: 33 · 2015: 4
- FWCI
- 26.13
- Type
- journal article
- Language
- en
- Update notices
- erratum (2015-11-17)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Chongqing University of Arts and Sciences
- National Heart, Lung, and Blood Institute (P01HL103453, U10HL109250)
- National Cancer Institute (P01CA062220)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-17A, IL-23, IL-17 receptor, act 1, γδ T cells, intestinal epithelial permeability, tight junctions, occludin, intestinal barrier integrity, colonic inflammation, intestinal injury, IL23R
- MeSH terms
- Acute Disease, Animals, Colitis, Colonic Neoplasms, Disease Models, Animal, Epithelium, Humans, Intestinal Mucosa, Permeability, Recombinant Proteins, Tumor Necrosis Factor-alpha, Lymphocyte Subsets, Dextran Sulfate, Receptors, Antigen, T-Cell, gamma-delta, Cell Polarity, Mice, Knockout, Homeodomain Proteins, Tight Junctions, Interleukin-17, Protein Transport, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Mice, Interleukin-23, Nuclear Receptor Subfamily 1, Group F, Member 3, Occludin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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