ArticleNature communications2025
Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells.
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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed.
- Article
- ZIF-8 nanoplatform coordinating ZnInternational journal of pharmaceutics: X · 2026Article
- PRMT5-mediated intron retention triggers innate and adaptive immunity against cancer.EMBO molecular medicine · 2026Article
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- Single-cell RNA sequencing of terminal ileal biopsies identifies signatures of Crohn's disease pathogenesis.Nature genetics · 2026Article
- Autoimmunity and peginterferon therapy for polycythemia vera.HemaSphere · 2026Review
- Coxsackievirus B escapes antiviral CD8Science advances · 2026Article
- Human iPSC-derived neurons stimulated with IFNγ present HLA class I-restricted antigens to cytotoxic CD8Journal of neuroinflammation · 2026Article
- Human neurons stimulated with IFNγ present HLA class I-restricted autoantigens to cytotoxic CD8bioRxiv : the preprint server for biology · 2026Article
- Type I Interferons as Contextual Regulators of B-Cell Tolerance in Type 1 Diabetes.Biomolecules · 2026Review
- Integrated histopathology of the human pancreas throughout stages of type 1 diabetes progression.Nature communications · 2026Article
- Insulin production is sustained during DNA damage-mediated senescence in adult human beta cells.Diabetologia · 2026Article
- Plasma EV miR-186-5p as an Early Biomarker and Regulator of IFN-α-Mediated Oxidative and β-Cell Dysfunction in Prediabetes.Antioxidants (Basel, Switzerland) · 2026Article
- Stress-driven remodeling of antigen presentation and chemokine signaling in pancreatic β-cells: implications for type 1 diabetes.Frontiers in immunology · 2026Review
- Neoepitopes at the crossroads of immunometabolism: metabolic remodeling of antigen presentation in type 1 diabetes.Frontiers in immunology · 2026Review
- Mechanisms and management of pegylated interferon-α toxicity in chronic hepatitis B.Frontiers in immunology · 2026Review
- Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Molecular and Inflammatory Etiologies of β-Cell Dysfunction in Type 1 Diabetes.Physiology (Bethesda, Md.) · 2025Review
- Islet-intrinsic sex differences in inflammatory signaling contribute to autoimmune diabetes susceptibility.bioRxiv : the preprint server for biology · 2025Article
- Article
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Authors and funding
30 authors.
Alexia CarréUniversité Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.ORCID http://orcid.org/0000-0001-8144-7194
Fatoumata Samassa *Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Zhicheng Zhou *Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.ORCID http://orcid.org/0000-0001-9137-7951
Javier Perez-HernandezUniversité Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.ORCID http://orcid.org/0000-0001-9712-2917
Christiana LekkaIslet Biology Group, Exeter Centre of Excellence in Diabetes Research, University of Exeter Medical School, Exeter, UK.
Anthony ManganaroDiabetes Center of Excellence, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Masaya OshimaUniversité Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Hanqing LiaoCentre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Robert ParkerCentre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Annalisa NicastriCentre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Barbara BrandaoUniversité Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Maikel L ColliULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium.
Decio L EizirikULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium.
Jahnavi AluriIndiana Biosciences Research Institute, Indianapolis, IN, USA.
Deep PatelIndiana Biosciences Research Institute, Indianapolis, IN, USA.
Marcus GöranssonDepartment of Health Technology, Technical University of Denmark, Copenhagen, Denmark.
Orlando Burgos MoralesUniversité Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Amanda AndersonBarbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
Laurie LandryBarbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
Farah KobaisiUniversité Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Raphael ScharfmannUniversité Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.ORCID http://orcid.org/0000-0001-7619-337X
Lorella MarselliDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID http://orcid.org/0000-0002-6698-2962
Piero MarchettiDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Sylvaine YouUniversité Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.ORCID http://orcid.org/0000-0002-1578-5205
Maki NakayamaBarbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
Sine R HadrupDepartment of Health Technology, Technical University of Denmark, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-5937-4344
Sally C KentDiabetes Center of Excellence, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-1543-8086
Sarah J RichardsonIslet Biology Group, Exeter Centre of Excellence in Diabetes Research, University of Exeter Medical School, Exeter, UK.ORCID http://orcid.org/0000-0002-1160-6062
Nicola TernetteCentre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-9283-0743
Roberto MalloneUniversité Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France. roberto.mallone@inserm.fr.ORCID http://orcid.org/0000-0002-9846-8861
Funding
The Human Islet Distribution Coordinating Center (UC4)UC4DK098085 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI EVANS-MOLINA, CARMELLA, NILAND, JOYCE CAROL · 2012 to 2017
$25.6MUniversity of Colorado Anschutz Medical Campus DRCP30DK116073 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI LORI SUSSEL · 2020 to 2026
$10.8MThe Integrated Stress Response in Human Islets During Early T1DU01DK127786 · NIDDK · UNIVERSITY OF CHICAGO · PI EVANS-MOLINA, CARMELLA, MIRMIRA, RAGHAVENDRA G · 2020 to 2025
$7.1MMolecular Dissection of Insulin Targeting in Anti-Islet AutoimmunityR01DK099317 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI AARON W MICHELS, Maki Nakayama · 2013 to 2026
$5.3MHumanized Mouse Avatars for T1DU01DK104218 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BREHM, MICHAEL ALLEN, GREINER, DALE LESLIE · 2019 to 2023
$4.5MImplications of Changes in Islet Exosomal Cargo in Type 1 DiabetesR01DK133881 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI EVANS-MOLINA, CARMELLA, MIRMIRA, RAGHAVENDRA G · 2022 to 2025
$2.7MiPLA2beta-mediated alternative splicing and -cell death in type 1 diabetesR01DK126444 · NIDDK · UNIVERSITY OF VIRGINIA · PI CHALFANT, CHARLES E., EIZIRIK, DECIO LAKS · 2021 to 2024
$2.0MHuman Islet-Infiltrating T Cell Biology: Reactivity, Structure, and FunctionUC4DK116284 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI HARLAN, DAVID MARSHALL, KENT, SALLY CHOATE · 2017 to 2017
$2.0MAgence Nationale de la Recherche (French National Research Agency) ANR-19-CE15-0014-01European Foundation for the Study of Diabetes (EFSD) EFSD/JDRF/Lilly European Programme in Type 1 Diabetes Research 2019European Foundation for the Study of Diabetes (EFSD) EFSD/Lilly Young Investigator Research Award Programme 2023Fondation pour la Recherche Médicale (Foundation for Medical Research in France) EQU20193007831JDRF 3-SRA-2022-1201-S-B, 5-SRA-2018-557-Q-R, Postdoctoral Fellowship 3-PDF-2020-942-A-NLeona M. and Harry B. Helmsley Charitable Trust (Helmsley Charitable Trust) 1901-03689, 2018PG-T1D053NIDDK NIH HHS P30 DK116073NIDDK NIH HHS R01 DK099317NIDDK NIH HHS R01 DK126444NIDDK NIH HHS R01 DK133881NIDDK NIH HHS U01 DK104218NIDDK NIH HHS U01 DK127786NIDDK NIH HHS UC4 DK098085NIDDK NIH HHS UC4 DK116284
Abstract
Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8
Indexed as
Antigen PresentationHLA-B AntigensInsulin-Secreting CellsInterferon-alphaAdultAlternative SplicingCD8-Positive T-LymphocytesDiabetes Mellitus, Type 1FemaleHumansMalePeptidesHLA-B AntigensInterferon-alphaPeptides
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