| First Author | Piñeros AR | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 13 | Pages | 111011 |
| PubMed ID | 35767947 | Mgi Jnum | J:326595 |
| Mgi Id | MGI:7311477 | Doi | 10.1016/j.celrep.2022.111011 |
| Citation | Pineros AR, et al. (2022) Proinflammatory signaling in islet beta cells propagates invasion of pathogenic immune cells in autoimmune diabetes. Cell Rep 39(13):111011 |
| abstractText | Type 1 diabetes is a disorder of immune tolerance that leads to death of insulin-producing islet beta cells. We hypothesize that inflammatory signaling within beta cells promotes progression of autoimmunity within the islet microenvironment. To test this hypothesis, we deleted the proinflammatory gene encoding 12/15-lipoxygenase (Alox15) in beta cells of non-obese diabetic mice at a pre-diabetic time point when islet inflammation is a feature. Deletion of Alox15 leads to preservation of beta cell mass, reduces populations of infiltrating T cells, and protects against spontaneous autoimmune diabetes in both sexes. Mice lacking Alox15 in beta cells exhibit an increase in a population of beta cells expressing the gene encoding the protein programmed death ligand 1 (PD-L1), which engages receptors on immune cells to suppress autoimmunity. Delivery of a monoclonal antibody against PD-L1 recovers the diabetes phenotype in knockout animals. Our results support the contention that inflammatory signaling in beta cells promotes autoimmunity during type 1 diabetes progression. |
