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PDL1 is Expressed in the Islets of People With Type 1 Diabetes and is Up-regulated by Interferons-α and-γ

19 Pages Posted: 1 Jun 2018 Publication Status: Under Review

See all articles by Maikel L. Colli

Maikel L. Colli

Université Libre de Bruxelles (ULB) - ULB Center for Diabetes Research

Jessica L. E. Hill

University of Exeter - Institute of Biomedical and Clinical Science

Laura Marroqui

Université Libre de Bruxelles (ULB) - ULB Center for Diabetes Research

Reinaldo S. Dos Santos

Université Libre de Bruxelles (ULB) - ULB Center for Diabetes Research

Alexandra Coomans de Brachène

Université Libre de Bruxelles (ULB) - ULB Center for Diabetes Research

Flavia M. M. Paula

Université Libre de Bruxelles (ULB) - ULB Center for Diabetes Research

Anne Op de Beeck

Université Libre de Bruxelles (ULB) - ULB Center for Diabetes Research

Lorella Marselli

University of Pisa - Islet Cell Laboratory

Piero Marchetti

University of Pisa - Islet Cell Laboratory

Noel G. Morgan

University of Exeter - Institute of Biomedical and Clinical Science

Sarah J. Richardson

University of Exeter - Institute of Biomedical and Clinical Science

Décio L. Eizirik

Université Libre de Bruxelles (ULB) - ULB Center for Diabetes Research; University of Pisa - Islet Cell Laboratory

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Abstract

Antibodies targeting PD-1 and its ligand PDL1 are used in cancer immunotherapy but may lead to autoimmune diseases, including type 1 diabetes (T1D). PD-1/PDL1 expression is probably important for maintaining tolerance, but it remains unclear whether PDL1 is expressed in pancreatic islets of people with T1D and how is it regulated in human beta cells. PDL1 was present in both insulin- and glucagon-positive cells from T1D individuals (3 children and 3 adults with T1D) but absent from insulin-deficient islets or from the islets of six non-diabetic controls. Interferons-α and -γ, but not interleukin-1β, induced PDL1 expression in vitro in human islet cells and EndoC-βH1 cells. Silencing of STAT2 did not prevent interferon-α-induced PDL1, while blocking of JAKs – a proposed therapeutic strategy for T1D – prevented PDL1 induction. The present findings indicate that PDL1 is expressed in beta cells from people with T1D, possibly to attenuate the autoimmune assault, and that it is induced by both type I and II interferons.

Keywords: type 1 diabetes, PDL1, pancreatic beta cells, pancreatic islets, apoptosis, immune checkpoint inhibitor

Suggested Citation

Colli, Maikel L. and Hill, Jessica L. E. and Marroqui, Laura and Dos Santos, Reinaldo S. and Coomans de Brachène, Alexandra and Paula, Flavia M. M. and Op de Beeck, Anne and Marselli, Lorella and Marchetti, Piero and Morgan, Noel G. and Richardson, Sarah J. and Eizirik, Décio L., PDL1 is Expressed in the Islets of People With Type 1 Diabetes and is Up-regulated by Interferons-α and-γ (2018). Available at SSRN: https://ssrn.com/abstract=3188385 or http://dx.doi.org/10.2139/ssrn.3188385
This version of the paper has not been formally peer reviewed.

Maikel L. Colli

Université Libre de Bruxelles (ULB) - ULB Center for Diabetes Research ( email )

U.L.B. CP618
Route de Lennik 808
Brussels, 1070
Belgium

Jessica L. E. Hill

University of Exeter - Institute of Biomedical and Clinical Science

Northcote House
The Queen's Drive
Exeter, Devon EX4 4QJ
United Kingdom

Laura Marroqui

Université Libre de Bruxelles (ULB) - ULB Center for Diabetes Research

U.L.B. CP618
Route de Lennik 808
Brussels, 1070
Belgium

Reinaldo S. Dos Santos

Université Libre de Bruxelles (ULB) - ULB Center for Diabetes Research

U.L.B. CP618
Route de Lennik 808
Brussels, 1070
Belgium

Alexandra Coomans de Brachène

Université Libre de Bruxelles (ULB) - ULB Center for Diabetes Research

U.L.B. CP618
Route de Lennik 808
Brussels, 1070
Belgium

Flavia M. M. Paula

Université Libre de Bruxelles (ULB) - ULB Center for Diabetes Research

U.L.B. CP618
Route de Lennik 808
Brussels, 1070
Belgium

Anne Op de Beeck

Université Libre de Bruxelles (ULB) - ULB Center for Diabetes Research

U.L.B. CP618
Route de Lennik 808
Brussels, 1070
Belgium

Lorella Marselli

University of Pisa - Islet Cell Laboratory

Pisa, 56126
Italy

Piero Marchetti

University of Pisa - Islet Cell Laboratory

Pisa, 56126
Italy

Noel G. Morgan

University of Exeter - Institute of Biomedical and Clinical Science

Northcote House
The Queen's Drive
Exeter, Devon EX4 4QJ
United Kingdom

Sarah J. Richardson

University of Exeter - Institute of Biomedical and Clinical Science

Northcote House
The Queen's Drive
Exeter, Devon EX4 4QJ
United Kingdom

Décio L. Eizirik (Contact Author)

Université Libre de Bruxelles (ULB) - ULB Center for Diabetes Research ( email )

U.L.B. CP618
Route de Lennik 808
Brussels, 1070
Belgium

University of Pisa - Islet Cell Laboratory ( email )

Pisa, 56126
Italy