Proinflammatory signaling in islet β cells propagates invasion of pathogenic immune cells in autoimmune diabetes
dc.contributor.author | Piñeros, Annie R. | |
dc.contributor.author | Kulkarni, Abhishek | |
dc.contributor.author | Gao, Hongyu | |
dc.contributor.author | Orr, Kara S. | |
dc.contributor.author | Glenn, Lindsey | |
dc.contributor.author | Huang, Fei | |
dc.contributor.author | Liu, Yunlong | |
dc.contributor.author | Gannon, Maureen | |
dc.contributor.author | Syed, Farooq | |
dc.contributor.author | Wu, Wenting | |
dc.contributor.author | Anderson, Cara M. | |
dc.contributor.author | Evans-Molina, Carmella | |
dc.contributor.author | McDuffie, Marcia | |
dc.contributor.author | Nadler, Jerry L. | |
dc.contributor.author | Morris, Margaret A. | |
dc.contributor.author | Mirmira, Raghavendra G. | |
dc.contributor.author | Tersey, Sarah A. | |
dc.contributor.department | Pediatrics, School of Medicine | |
dc.date.accessioned | 2023-07-26T15:22:35Z | |
dc.date.available | 2023-07-26T15:22:35Z | |
dc.date.issued | 2022 | |
dc.description.abstract | Type 1 diabetes is a disorder of immune tolerance that leads to death of insulin-producing islet β cells. We hypothesize that inflammatory signaling within β cells promotes progression of autoimmunity within the islet microenvironment. To test this hypothesis, we deleted the proinflammatory gene encoding 12/15-lipoxygenase (Alox15) in β 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 β cell mass, reduces populations of infiltrating T cells, and protects against spontaneous autoimmune diabetes in both sexes. Mice lacking Alox15 in β cells exhibit an increase in a population of β 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 β cells promotes autoimmunity during type 1 diabetes progression. | |
dc.eprint.version | Author's manuscript | |
dc.identifier.citation | Piñeros AR, Kulkarni A, Gao H, et al. Proinflammatory signaling in islet β cells propagates invasion of pathogenic immune cells in autoimmune diabetes. Cell Rep. 2022;39(13):111011. doi:10.1016/j.celrep.2022.111011 | |
dc.identifier.uri | https://hdl.handle.net/1805/34576 | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | |
dc.relation.isversionof | 10.1016/j.celrep.2022.111011 | |
dc.relation.journal | Cell Reports | |
dc.rights | Publisher Policy | |
dc.source | PMC | |
dc.subject | Metabolism | |
dc.subject | Immune checkpoint | |
dc.subject | Immunology | |
dc.subject | Insulin | |
dc.subject | Islet | |
dc.subject | Pancreas | |
dc.subject | Single-cell RNA sequencing | |
dc.subject | Type 1 diabetes | |
dc.title | Proinflammatory signaling in islet β cells propagates invasion of pathogenic immune cells in autoimmune diabetes | |
dc.type | Article |