| First Author | Osum KC | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 8295 |
| PubMed ID | 29844327 | Mgi Jnum | J:263367 |
| Mgi Id | MGI:6163465 | Doi | 10.1038/s41598-018-26471-9 |
| Citation | Osum KC, et al. (2018) Interferon-gamma drives programmed death-ligand 1 expression on islet beta cells to limit T cell function during autoimmune diabetes. Sci Rep 8(1):8295 |
| abstractText | Type 1 diabetes is caused by autoreactive T cell-mediated beta cell destruction. Even though co-inhibitory receptor programmed death-1 (PD-1) restrains autoimmunity, the expression and regulation of its cognate ligands on beta cell remains unknown. Here, we interrogated beta cell-intrinsic programmed death ligand-1 (PD-L1) expression in mouse and human islets. We measured a significant increase in the level of PD-L1 surface expression and the frequency of PD-L1(+) beta cells as non-obese diabetic (NOD) mice aged and developed diabetes. Increased beta cell PD-L1 expression was dependent on T cell infiltration, as beta cells from Rag1-deficient mice lacked PD-L1. Using Rag1-deficient NOD mouse islets, we determined that IFN-gamma promotes beta cell PD-L1 expression. We performed analogous experiments using human samples, and found a significant increase in beta cell PD-L1 expression in type 1 diabetic samples compared to type 2 diabetic, autoantibody positive, and non-diabetic samples. Among type 1 diabetic samples, beta cell PD-L1 expression correlated with insulitis. In vitro experiments with human islets from non-diabetic individuals showed that IFN-gamma promoted beta cell PD-L1 expression. These results suggest that insulin-producing beta cells respond to pancreatic inflammation and IFN-gamma production by upregulating PD-L1 expression to limit self-reactive T cells. |
