The DOI matches its Crossref record; 109 of the 109 references it cites were found in a registry or an index.
Regulatory T cell dysfunction in type 1 diabetes: what's broken and how can we fix it?
Open accessAbstract
Type 1 diabetes is an autoimmune disease characterised by the destruction of insulin producing beta cells in the pancreas. Whilst it remains unclear what the original triggering factors for this destruction are, observations from the natural history of human type 1 diabetes, including incidence rates in twins, suggest that the disease results from a combination of genetic and environmental factors. Whilst many different immune cells have been implicated, including members of the innate and adaptive immune systems, a view has emerged over the past 10 years that beta cell damage is mediated by the combined actions of CD4 + and CD8 + T cells with specificity for islet autoantigens. In health, these potentially pathogenic T cells are held in check by multiple regulatory mechanisms, known collectively as ‘immunological tolerance’. This raises the question as to whether type 1 diabetes develops, at least in part, as a result of a defect in one or more of these control mechanisms. Immunological tolerance includes both central mechanisms (purging of the T cell repertoire of high-affinity autoreactive T cells in the thymus) and peripheral mechanisms, a major component of which is the action of a specialised subpopulation of T cells, known as regulatory T cells (Tregs). In this review, we highlight the evidence suggesting that a reduction in the functional capacity of different Treg populations contributes to disease development in type 1 diabetes. We also address current controversies regarding the putative causes of this defect and discuss strategies to correct it as a means to reduce or prevent islet destruction in a clinical setting.
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“The pathogenesis of type 1 diabetes results from a complex interaction between the pancreatic β-cell and innate and adaptive immune systems (figure 3).47”
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Metadata
- Authors
- Hull, C. M., Peakman, M., & Tree, T. I. M.
- Affiliations
- Guy's Hospital (GB)
- Corresponding author
- Hull, Caroline M.
- Tree, Timothy I. M.
- Venue
- Diabetologia
- Published
- 2017-08-02
- Volume
- 60
- Issue
- 10
- Pages
- 1839-1850
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC6448885
- OpenAlex
- W2739639576
- Cited by
- 194
- References
- 109
- Citations by year
- 2026: 11 · 2025: 32 · 2024: 30 · 2023: 17 · 2022: 25 · 2021: 25 · 2020: 21 · 2019: 19 · 2018: 13 · 2017: 1
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Diabetologia (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, cc-by)
- Funders
- King's College London
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- type 1 diabetes, regulatory T cells, immune tolerance, beta cell destruction, islet autoantigens, CD4+ T cells, CD8+ T cells, thymic selection, peripheral tolerance, Treg dysfunction, Treg therapy, autoimmunity
- MeSH terms
- Animals, Diabetes Mellitus, Type 1, Humans, Immune Tolerance, T-Lymphocytes, Regulatory
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