What the HLA-I! – Classical and non-classical HLA Class I and their potential roles in type 1 diabetes
dc.contributor.author | Wyatt, R | |
dc.contributor.author | Lanzoni, G | |
dc.contributor.author | Russell, MA | |
dc.contributor.author | Gerling, I | |
dc.contributor.author | Richardson, SJ | |
dc.date.accessioned | 2019-09-16T08:29:19Z | |
dc.date.issued | 2019-12-09 | |
dc.description.abstract | Purpose of review: Hyperexpression of classical HLA class I (HLA-I) molecules in insulincontaining islets has become a widely accepted hallmark of type 1 diabetes pathology. In comparison, relatively little is known about the expression, function and role of non-classical subtypes of HLA-I. This review focuses on current understanding of the non-classical HLA-I subtypes: HLA-E, HLA-F and HLA-G, within and outside the field of type 1 diabetes, and considers the possible impacts of these molecules on disease etiology. Recent Findings: Evidence is growing to suggest that non-classical HLA-I proteins are upregulated, both at the RNA and protein level in the pancreas of individuals with recent-onset type 1 diabetes. Moreover, associations between non-classical HLA-I genotypes and age at onset of type 1 diabetes have been reported in some studies. As with classical HLA-I, it is likely that hyperexpression of non-classical HLA-I is driven by the release of diffusible interferons by stressed β cells (potentially driven by viral infection) and exacerbated by release of cytokines from infiltrating immune cells. Summary: Non-classical HLA-I proteins predominantly (but not exclusively) transduce negative signals to immune cells infiltrating at the site of injury/inflammation. We propose a model in which the islet endocrine cells through expression of non-classical HLA-I are fighting back against the infiltrating immune cells. By inhibiting the activity and function on NK, B, and select T cells the non-classical HLA-I proteins will reduce the non-specific bystander effects of inflammation, whilst at the same time still allowing the targeted destruction of β cells by specific islet-reactive CD8+ T cells. | en_GB |
dc.description.sponsorship | Juvenile Diabetes Research Foundation International | en_GB |
dc.description.sponsorship | Diabetes UK | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | Diabetes UK | en_GB |
dc.description.sponsorship | Juvenile Diabetes Research Foundation International | en_GB |
dc.identifier.citation | Vol. 19, article 159 | en_GB |
dc.identifier.doi | 10.1007/s11892-019-1245-z | |
dc.identifier.grantnumber | MR/N027973/1 | en_GB |
dc.identifier.grantnumber | 14/224/04 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/38761 | |
dc.language.iso | en | en_GB |
dc.publisher | Springer | en_GB |
dc.rights | © The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | |
dc.subject | Type 1 diabetes | en_GB |
dc.subject | HLA-I | en_GB |
dc.subject | non-classical HLA-I | en_GB |
dc.subject | HLA-E | en_GB |
dc.subject | HLA-F | en_GB |
dc.subject | HLA-G | en_GB |
dc.subject | immune system | en_GB |
dc.title | What the HLA-I! – Classical and non-classical HLA Class I and their potential roles in type 1 diabetes | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-09-16T08:29:19Z | |
dc.identifier.issn | 1534-4827 | |
dc.description | This is the final version. Available on open access from Springer via the DOI in this record | en_GB |
dc.identifier.journal | Current Diabetes Reports | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | en_GB |
dcterms.dateAccepted | 2019-08-23 | |
exeter.funder | ::Juvenile Diabetes Research Foundation International | en_GB |
exeter.funder | ::Diabetes UK | en_GB |
exeter.funder | ::Medical Research Council (MRC) | en_GB |
exeter.funder | ::Diabetes UK | en_GB |
exeter.funder | ::Juvenile Diabetes Research Foundation International | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2019-08-23 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-09-14T07:10:06Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2020-02-12T11:16:58Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.