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.

Autor:	Russell MA; Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, U.K., Redick SD; Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA., Blodgett DM; Division of Diabetes, Department of Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA.; Math and Science Division, Babson College, Wellesley, MA., Richardson SJ; Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, U.K., Leete P; Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, U.K., Krogvold L; Pediatric Department, Oslo University Hospital, and Faculty of Medicine, University of Oslo, Oslo, Norway., Dahl-Jørgensen K; Pediatric Department, Oslo University Hospital, and Faculty of Medicine, University of Oslo, Oslo, Norway., Bottino R; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA., Brissova M; Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., Spaeth JM; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN., Babon JAB; Division of Diabetes, Department of Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA., Haliyur R; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN., Powers AC; Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN.; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN., Yang C; Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA., Kent SC; Division of Diabetes, Department of Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA., Derr AG; Program in Bioinformatics, University of Massachusetts Medical School, Worcester, MA., Kucukural A; Program in Bioinformatics, University of Massachusetts Medical School, Worcester, MA., Garber MG; Program in Bioinformatics, University of Massachusetts Medical School, Worcester, MA., Morgan NG; Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, U.K., Harlan DM; Division of Diabetes, Department of Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA david.harlan@umassmemorial.org.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2019 May; Vol. 68 (5), pp. 988-1001. Date of Electronic Publication: 2019 Mar 04.
DOI:	10.2337/db18-0686
Abstrakt:	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. (© 2019 by the American Diabetes Association.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu