Abstract:
:Type 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.
journal_name
Diabetesjournal_title
Diabetesauthors
Russell MA,Redick SD,Blodgett DM,Richardson SJ,Leete P,Krogvold L,Dahl-Jørgensen K,Bottino R,Brissova M,Spaeth JM,Babon JAB,Haliyur R,Powers AC,Yang C,Kent SC,Derr AG,Kucukural A,Garber MG,Morgan NG,Harlan DMdoi
10.2337/db18-0686subject
Has Abstractpub_date
2019-05-01 00:00:00pages
988-1001issue
5eissn
0012-1797issn
1939-327Xpii
db18-0686journal_volume
68pub_type
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