Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder
Open accessAbstract
Coeliac disease is a common small bowel enteropathy arising in genetically predisposed individuals and caused by ingestion of gluten in the diet. Great advances have been made in understanding the role of the adaptive immune system in response to gluten peptides. Despite detailed knowledge of these adaptive immune mechanisms, the complete series of pathogenic events responsible for development of the tissue lesion remains less certain. This review contributes to the field by discussing additional mechanisms which may also contribute to pathogenesis. These include the production of cytokines such as interleukin-15 by intestinal epithelial cells and local antigen presenting cells as a pivotal event in the disease process. A subset of unconventional T cells called gamma/delta T cells are also persistently expanded in the coeliac disease (CD) small intestinal epithelium and recent analysis has shown that these cells contribute to pathogenic inflammation. Other unconventional T cell subsets may play a local immunoregulatory role and require further study. It has also been suggested that, in addition to activation of pathogenic T helper cells by gluten peptides, other peptides may directly interact with the intestinal mucosa, further contributing to the disease process. We also discuss how myofibroblasts, a major source of tissue transglutaminase and metalloproteases, may play a key role in intestinal tissue remodeling. Contribution of each of these factors to pathogenesis is discussed to enhance our view of this complex disorder and to contribute to a wider understanding of chronic immune-mediated disease.
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The growth of dermal γδ T cells preferentially requires IL-7, whereas IL-15 is mandatory for the generation of γδ TCR-expressing intra-epithelial lymphocytes (IELs).
“The growth of dermal γδ T cells preferentially requires IL-7, whereas IL-15 is mandatory for the generation of γδ TCR-expressing intra-epithelial lymphocytes (IELs) (13).”
From Comparing Mouse and Human Tissue-Resident γδ T Cells (2022) · cites this paper as [13]
The section “A Role for Conventional and Unconventional Lymphocytes?” discusses γδ IELs and links IL-15 to activation and expansion of cytolytic CD8 IELs, but it does not state that IL-15 is mandatory for generating γδ TCR-expressing IELs. Searches for dermal γδ T-cell growth and IL-7 also found no passage addressing the claimed requirement. (LLM, conf=0.70)
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- Authors
- Dunne, M. R., Byrne, G., Chirdo, F. G., & Feighery, C.
- Affiliations
- Trinity College Dublin (IE)
- Technological University Dublin (IE)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Corresponding author
- Byrne, Greg
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2020-07-08
- Volume
- 11
- Pages
- 1374-1374
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC7360848
- OpenAlex
- W3041687278
- Cited by
- 85
- References
- 172
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 13 · 2023: 9 · 2022: 16 · 2021: 16 · 2020: 1
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Arrow - TU Dublin (Technological University Dublin) (submittedVersion, cc-by-nc-sa)
- El Servicio de Difusión de la Creación Intelectual (National University of La Plata) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Conicet (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Wheat and Barley Genetics and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- celiac disease, pathogenesis, gluten, adaptive immune response, IL-15, antigen-presenting cells, γδ T cells, unconventional T cells, tissue transglutaminase, myofibroblasts, intestinal mucosa
- MeSH terms
- Celiac Disease, Humans, Immunity, Innate, Adaptive Immunity
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