The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease
Open accessAbstract
Coeliac disease is a complex, polygenic inflammatory enteropathy caused by exposure to dietary gluten that occurs in a subset of genetically susceptible individuals who express either the HLA-DQ8 or HLA-DQ2 haplotypes 1,2. The need to develop non-dietary treatments is now widely recognized 3, but no pathophysiologically relevant gluten- and HLA-dependent preclinical model exists. Furthermore, although studies in humans have led to major advances in our understanding of the pathogenesis of coeliac disease 4, the respective roles of disease-predisposing HLA molecules, and of adaptive and innate immunity in the development of tissue damage, have not been directly demonstrated. Here we describe a mouse model that reproduces the overexpression of interleukin-15 (IL-15) in the gut epithelium and lamina propria that is characteristic of active coeliac disease, expresses the predisposing HLA-DQ8 molecule, and develops villous atrophy after ingestion of gluten. Overexpression of IL-15 in both the epithelium and the lamina propria is required for the development of villous atrophy, which demonstrates the location-dependent central role of IL-15 in the pathogenesis of coeliac disease. In addition, CD4+ T cells and HLA-DQ8 have a crucial role in the licensing of cytotoxic T cells to mediate intestinal epithelial cell lysis. We also demonstrate a role for the cytokine interferon-γ (IFNγ) and the enzyme transglutaminase 2 (TG2) in tissue destruction. By reflecting the complex interaction between gluten, genetics and IL-15-driven tissue inflammation, this mouse model provides the opportunity to both increase our understanding of coeliac disease, and develop new therapeutic strategies.
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“Under stress or inflammatory conditions, such as in celiac disease, iIELs upregulate the expression of activating NKG2D and CD94/NKG2C receptors, (which recognize MICA/B and HLA-E, respectively) while losing the expression of the inhibitory receptors CD94/NKG2A [302, 306-308].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [308]
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Near-optimal probabilistic RNA-seq quantification
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Husby, S., Koletzko, S., Korponay‐Szabó, I. R., Mearin, M. L., Phillips, A., Shamir, R., Troncone, R., Giersiepen, K., Branski, D., Catassi, C., et al. (2012) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0b013e31821a23d0 · Cited by 2,683
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lumi : a pipeline for processing Illumina microarray
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Identification of tissue transglutaminase as the autoantigen of celiac disease
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Cossarizza, A., Chang, H., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andrä, I., Andreata, F., Annunziato, F., Arranz, E., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202170126 · Cited by 531
KIR + CD8 + T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19
Li, J., Zaslavsky, M., Su, Y., Guo, J., Sikora, M. J., van Unen, V., Christophersen, A., Chiou, S.-H., Chen, L., Li, J., et al. (2022) · Science · doi:10.1126/science.abi9591 · Cited by 249
Self-citationA Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease
Schuppan, D., Mäki, M., Lundin, K. E. A., Isola, J. J., Friesing-Sosnik, T., Taavela, J., Popp, A., Koskenpato, J., Langhorst, J., Hovde, Ø., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2032441 · Cited by 234
The Immunobiology and Pathogenesis of Celiac Disease
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Lamas, B., Hernandez-Galan, L., Galipeau, H. J., Constante, M., Clarizio, A., Jury, J., Breyner, N. M., Caminero, A., Rueda, G., Hayes, C. L., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aba0624 · Cited by 179
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Metadata
- Authors
- Abadie, V., Kim, S. M., Lejeune, T., Palanski, B. A., Ernest, J. D., Tastet, O., Voisine, J., Discepolo, V., Marietta, E. V., Hawash, M. B. F., Ciszewski, C., Bouziat, R., Panigrahi, K., Horwath, I., Zurenski, M. A., Lawrence, I., Dumaine, A., Yotova, V., Grenier, J.-C., Murray, J. A., Khosla, C., Barreiro, L. B., & Jabri, B.
- Affiliations
- University of Chicago (US)
- Université de Montréal (CA)
- Stanford University (US)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Mayo Clinic (US)
- ORCID
- Venue
- Nature
- Published
- 2020-02-12
- Volume
- 578
- Issue
- 7796
- Pages
- 600-604
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7047598
- OpenAlex
- W3005574648
- Cited by
- 231
- References
- 43
- Citations by year
- 2026: 21 · 2025: 52 · 2024: 39 · 2023: 27 · 2022: 33 · 2021: 32 · 2020: 25
- FWCI
- 26.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (T32AI007090)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100619, T32DK007074, R01DK067180, P30DK042086, R01DK063158)
- Topics
- Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Wheat and Barley Genetics and Pathology
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Keywords
- celiac disease, IL-15, gluten, HLA-DQ8, villous atrophy, mouse model, CD4+ T cells, cytotoxic T lymphocytes, interferon-gamma, tissue transglutaminase, intestinal epithelial damage, lamina propria, HLA-DQ2, innate immunity, adaptive immunity
- MeSH terms
- Animals, Celiac Disease, Female, Glutens, HLA-DQ Antigens, Humans, Interferon-gamma, Male, Mice, Transgenic, Microfilament Proteins, CD4-Positive T-Lymphocytes, Interleukin-15, Mice
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