IFN-α induces a preferential long-lasting expression of MHC class I in human pancreatic beta cells

  • Alexandra Coomans de Brachène
  • Reinaldo S. Dos Santos
  • Laura Marroqui
  • Maikel L. Colli
  • Lorella Marselli
  • Raghavendra G. Mirmira
  • Piero Marchetti
  • Decio L. Eizirik
Short Communication



IFN-α, a cytokine expressed in human islets from individuals affected by type 1 diabetes, plays a key role in the pathogenesis of diabetes by upregulating inflammation, endoplasmic reticulum (ER) stress and MHC class I overexpression, three hallmarks of islet histology in early type 1 diabetes. We tested whether expression of these mediators of beta cell loss is reversible upon IFN-α withdrawal or IFN-α pathway inhibition.


IFN-α-induced MHC class I overexpression, ER stress and inflammation were evaluated by flow cytometry, immunofluorescence and real-time PCR in human EndoC-βH1 cells or human islets exposed to IFN-α with or without the presence of Janus kinase (JAK) inhibitors. Protein expression was evaluated by western blot.


IFN-α-induced expression of inflammatory and ER stress markers returned to baseline after 24–48 h following cytokine removal. In contrast, MHC class I overexpression at the cell surface persisted for at least 7 days. Treatment with JAK inhibitors, when added with IFN-α, prevented MHC class I overexpression, but when added 24 h after IFN-α exposure these inhibitors failed to accelerate MHC class I return to baseline.


IFN-α mediates a long-lasting and preferential MHC class I overexpression in human beta cells, which is not affected by the subsequent addition of JAK inhibitors. These observations suggest that IFN-α-stimulated long-lasting MHC class I expression may amplify beta cell antigen presentation during the early phase of type 1 diabetes and that IFN-α inhibitors might need to be used at very early stages of the disease to be effective.


IFN-α JAK inhibitors MHC class I Pancreatic beta cells Pancreatic islets Type 1 diabetes 



Binding immunoglobulin protein


CCAAT/enhancer-binding protein homologous protein




C-X-C motif chemokine ligand 10


Endoplasmic reticulum


Janus kinase


MX dynamin-like GTPase 1


Signal transducer and activator of transcription


Tyrosine kinase 2



The authors are grateful to A. Op de Beeck for advice and help on the FACS analysis, and M. Pangerl, A.M. Musuaya, N. Pachera, Y. Cai and I. Millard of the ULB Center for Diabetes Research, Université Libre de Bruxelles, Belgium, for excellent technical support.

Contribution statement

ACdB and RSS contributed to the original idea and the design of the experiments, researched data, contributed to discussion, and wrote, revised, and edited the manuscript. LM, MLC, LoM and PM researched data and revised and edited the manuscript. RGM contributed to the original idea, experimental design and interpretation of the experiments, and revised and edited the manuscript. DLE contributed to the original idea and the design and interpretation of the experiments, contributed to discussion, and wrote, revised and edited the manuscript. All authors have read and approved the final version of the manuscript, and gave informed consent. ACdB and DLE are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2017_4536_MOESM1_ESM.pdf (3.6 mb)
ESM (PDF 3.63 mb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.ULB Center for Diabetes Research, Medical Faculty, Campus ErasmeUniversité Libre de BruxellesBrusselsBelgium
  2. 2.CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) and Institute of BioengineeringMiguel Hernández University of ElcheAlicanteSpain
  3. 3.Department of Clinical and Experimental MedicineUniversity of PisaPisaItaly
  4. 4.Department of Pediatrics, Medicine, and Physiology, Center for Diabetes and Metabolic DiseasesIndiana University School of Medicine, School of MedicineIndianapolisUSA

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