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- Title
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.
- Authors
Russell, Mark A.; Richardson, Sarah J.; Leete, Pia; Morgan, Noel G.; Derr, Alan G.; Kucukural, Alper; Garber, Manuel G.; Yang, Chaoxing; Redick, Sambra D.; Chaoxing Yang; Babon, Jenny Aurielle B.; Kent, Sally C.; Harlan, David M.; Blodgett, David M.; Krogvold, Lars; Dahl-Jørgensen, Knut; Bottino, Rita; Brissova, Marcela; Powers, Alvin C.; Spaeth, Jason M.
- 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.
- Subjects
TYPE 1 diabetes; ANTIGEN presentation; ANTIGEN processing; PROTEIN analysis; ISLANDS of Langerhans; ANTIGENS; CELL culture; CELLULAR immunity; COMPARATIVE studies; HISTOCOMPATIBILITY antigens; IMMUNITY; INSULIN; RESEARCH methodology; MEDICAL cooperation; RESEARCH; T cells; EVALUATION research
- Publication
Diabetes, 2019, Vol 68, Issue 5, p988
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db18-0686