PDL1 is expressed in the islets of people with type 1 diabetes and is up-regulated by interferons-α and-γ via IRF1 induction

PDL1 在 1 型糖尿病患者的胰岛中表达,并通过 IRF1 诱导由干扰素-α 和-γ 上调

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作者:Maikel L Colli, Jessica L E Hill, Laura Marroquí, Jessica Chaffey, Reinaldo S Dos Santos, Pia Leete, Alexandra Coomans de Brachène, Flavia M M Paula, Anne Op de Beeck, Angela Castela, Lorella Marselli, Lars Krogvold, Knut Dahl-Jorgensen, Piero Marchetti, Noel G Morgan, Sarah J Richardson, Décio L Ei

Background

Antibodies targeting PD-1 and its ligand PDL1 are used in cancer immunotherapy but may lead to autoimmune diseases, including type 1 diabetes (T1D). It remains unclear whether PDL1 is expressed in pancreatic islets of people with T1D and how is it regulated.

Methods

The expression of PDL1, IRF1, insulin and glucagon was evaluated in samples of T1D donors by immunofluorescence. Cytokine-induced PDL1 expression in the human beta cell line, EndoC-βH1, and in primary human pancreatic islets was determined by real-time RT-PCR, flow cytometry and Western blot. Specific and previously validated small interference RNAs were used to inhibit STAT1, STAT2, IRF1 and JAK1 signaling. Key

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