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dc.contributor.authorMorgan, Noel
dc.date.accessioned2019-05-09T14:45:34Z
dc.date.available2019-05-09T14:45:34Z
dc.date.issued2019-05
dc.identifier.citationRussell MA [et al]. HLA Class II Antigen Processing and Presentation Pathway Components Demonstrated by Transcriptome and Protein Analyses of Islet β-Cells From Donors With Type 1 Diabetes. Diabetes. 2019 May;68(5):988-1001en_US
dc.identifier.pmid30833470
dc.identifier.doi10.2337/db18-0686
dc.identifier.urihttps://rde.dspace-express.com/handle/123456789/620996
dc.description.abstractType 1 diabetes studies consistently generate data showing islet β-cell dysfunction and T cell-mediated anti-β-cell-specific autoimmunity. To explore the pathogenesis, we interrogated the β-cell transcriptomes from donors with and without type 1 diabetes using both bulk-sorted and single β-cells. Consistent with immunohistological studies, β-cells from donors with type 1 diabetes displayed increased Class I transcripts and associated mRNA species. These β-cells also expressed mRNA for Class II and Class II antigen presentation pathway components, but lacked the macrophage marker CD68. Immunohistological study of three independent cohorts of donors with recent-onset type 1 diabetes showed Class II protein and its transcriptional regulator Class II MHC trans-activator protein expressed by a subset of insulin+CD68- β-cells, specifically found in islets with lymphocytic infiltrates. β-Cell surface expression of HLA Class II was detected on a portion of CD45-insulin+ β-cells from donors with type 1 diabetes by immunofluorescence and flow cytometry. Our data demonstrate that pancreatic β-cells from donors with type 1 diabetes express Class II molecules on selected cells with other key genes in those pathways and inflammation-associated genes. β-Cell expression of Class II molecules suggests that β-cells may interact directly with islet-infiltrating CD4+ T cells and may play an immunopathogenic role.en_US
dc.language.isoenen_US
dc.publisherAmerican Diabetes Associationen_US
dc.relation.urlhttp://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=30833470en_US
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen_US
dc.titleHLA Class II Antigen Processing and Presentation Pathway Components Demonstrated by Transcriptome and Protein Analyses of Islet β-Cells From Donors With Type 1 Diabetesen_US
dc.typeJournal Articleen_US
dc.identifier.journalDiabetesen_US
dc.type.versionPublisheden_US


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