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

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.