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.


Journal

Diabetes
ISSN: 1939-327X
Titre abrégé: Diabetes
Pays: United States
ID NLM: 0372763

Informations de publication

Date de publication:
05 2019
Historique:
received: 20 06 2018
accepted: 25 02 2019
pubmed: 6 3 2019
medline: 19 11 2019
entrez: 6 3 2019
Statut: ppublish

Résumé

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

Identifiants

pubmed: 30833470
pii: db18-0686
doi: 10.2337/db18-0686
pmc: PMC6477908
doi:

Substances chimiques

Histocompatibility Antigens Class II 0
Insulin 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

988-1001

Subventions

Organisme : NIDDK NIH HHS
ID : P60 DK020593
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK104211
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK108120
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK116284
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK112232
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020593
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK105837
Pays : United States
Organisme : NIDDK NIH HHS
ID : R24 DK106755
Pays : United States

Informations de copyright

© 2019 by the American Diabetes Association.

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Auteurs

Mark A Russell (MA)

Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, U.K.

Sambra D Redick (SD)

Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA.

David M 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.

Sarah J Richardson (SJ)

Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, U.K.

Pia Leete (P)

Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, U.K.

Lars Krogvold (L)

Pediatric Department, Oslo University Hospital, and Faculty of Medicine, University of Oslo, Oslo, Norway.

Knut Dahl-Jørgensen (K)

Pediatric Department, Oslo University Hospital, and Faculty of Medicine, University of Oslo, Oslo, Norway.

Rita Bottino (R)

Institute of Cellular Therapeutics, Allegheny-Singer Research Institute Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA.

Marcela Brissova (M)

Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.

Jason M Spaeth (JM)

Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN.

Jenny Aurielle B Babon (JAB)

Division of Diabetes, Department of Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA.

Rachana Haliyur (R)

Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN.

Alvin C 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.

Chaoxing Yang (C)

Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA.

Sally C Kent (SC)

Division of Diabetes, Department of Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA.

Alan G Derr (AG)

Program in Bioinformatics, University of Massachusetts Medical School, Worcester, MA.

Alper Kucukural (A)

Program in Bioinformatics, University of Massachusetts Medical School, Worcester, MA.

Manuel G Garber (MG)

Program in Bioinformatics, University of Massachusetts Medical School, Worcester, MA.

Noel G Morgan (NG)

Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, U.K.

David M Harlan (DM)

Division of Diabetes, Department of Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA david.harlan@umassmemorial.org.

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