An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells

Maikel L. Colli (), Mireia Ramos-Rodríguez, Ernesto S. Nakayasu, Maria I. Alvelos, Miguel Lopes, Jessica L. E. Hill, Jean-Valery Turatsinze, Alexandra Coomans de Brachène, Mark A. Russell, Helena Raurell-Vila, Angela Castela, Jonàs Juan-Mateu, Bobbie-Jo M. Webb-Robertson, Lars Krogvold, Knut Dahl-Jorgensen, Lorella Marselli, Piero Marchetti, Sarah J. Richardson, Noel G. Morgan, Thomas O. Metz, Lorenzo Pasquali and Décio L. Eizirik
Additional contact information
Maikel L. Colli: Université Libre de Bruxelles
Mireia Ramos-Rodríguez: University Pompeu Fabra
Ernesto S. Nakayasu: Pacific Northwest National Laboratory
Maria I. Alvelos: Université Libre de Bruxelles
Miguel Lopes: Université Libre de Bruxelles
Jessica L. E. Hill: University of Exeter Medical School
Jean-Valery Turatsinze: Université Libre de Bruxelles
Alexandra Coomans de Brachène: Université Libre de Bruxelles
Mark A. Russell: University of Exeter Medical School
Helena Raurell-Vila: University Pompeu Fabra
Angela Castela: Université Libre de Bruxelles
Jonàs Juan-Mateu: Université Libre de Bruxelles
Bobbie-Jo M. Webb-Robertson: Pacific Northwest National Laboratory
Lars Krogvold: Oslo University Hospital
Knut Dahl-Jorgensen: Oslo University Hospital
Lorella Marselli: Islet Cell Laboratory, University of Pisa
Piero Marchetti: Islet Cell Laboratory, University of Pisa
Sarah J. Richardson: University of Exeter Medical School
Noel G. Morgan: University of Exeter Medical School
Thomas O. Metz: Pacific Northwest National Laboratory
Lorenzo Pasquali: University Pompeu Fabra
Décio L. Eizirik: Université Libre de Bruxelles

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract Interferon-α (IFNα), a type I interferon, is expressed in the islets of type 1 diabetic individuals, and its expression and signaling are regulated by T1D genetic risk variants and viral infections associated with T1D. We presently characterize human beta cell responses to IFNα by combining ATAC-seq, RNA-seq and proteomics assays. The initial response to IFNα is characterized by chromatin remodeling, followed by changes in transcriptional and translational regulation. IFNα induces changes in alternative splicing (AS) and first exon usage, increasing the diversity of transcripts expressed by the beta cells. This, combined with changes observed on protein modification/degradation, ER stress and MHC class I, may expand antigens presented by beta cells to the immune system. Beta cells also up-regulate the checkpoint proteins PDL1 and HLA-E that may exert a protective role against the autoimmune assault. Data mining of the present multi-omics analysis identifies two compound classes that antagonize IFNα effects on human beta cells.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-16327-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16327-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-16327-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().