{"doi":"10.1016/j.celrep.2022.111011","title":"Proinflammatory signaling in islet β cells propagates invasion of pathogenic immune cells in autoimmune diabetes","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.","journal":"Cell Reports","year":2022,"id":242057,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":370035,"name":"Abhishek Kulkarni","orcid":"0000-0001-6792-7183","position":1,"is_corresponding":false},{"id":29086,"name":"Hongyu Gao","orcid":"0000-0001-8633-3604","position":2,"is_corresponding":false},{"id":382490,"name":"Kara S. Orr","orcid":"0000-0002-1321-8581","position":3,"is_corresponding":false},{"id":696308,"name":"Lindsey Glenn","orcid":"0000-0002-8543-6684","position":4,"is_corresponding":false},{"id":872269,"name":"Fei Huang","orcid":"0000-0001-9769-4798","position":5,"is_corresponding":false},{"id":227678,"name":"Yunlong Liu","orcid":"0000-0002-2699-626X","position":6,"is_corresponding":false},{"id":304325,"name":"Maureen Gannon","orcid":"0000-0003-3287-8101","position":7,"is_corresponding":false},{"id":251261,"name":"Farooq Syed","orcid":"0000-0002-0284-0631","position":8,"is_corresponding":false},{"id":57841,"name":"Wenting Wu","orcid":"0000-0003-0982-771X","position":9,"is_corresponding":false},{"id":873104,"name":"Cara M. Anderson","orcid":null,"position":10,"is_corresponding":false},{"id":7388,"name":"Carmella Evans‐Molina","orcid":"0000-0001-7764-8663","position":11,"is_corresponding":false},{"id":873105,"name":"Marcia McDuffie","orcid":null,"position":12,"is_corresponding":false},{"id":439667,"name":"Jerry L. Nadler","orcid":"0000-0002-4200-6991","position":13,"is_corresponding":false},{"id":872270,"name":"Margaret Morris","orcid":"0000-0003-2399-6552","position":14,"is_corresponding":false},{"id":244409,"name":"Raghavendra G. Mirmira","orcid":"0000-0002-5013-6075","position":15,"is_corresponding":false},{"id":244408,"name":"Sarah A. Tersey","orcid":"0000-0003-0667-2361","position":16,"is_corresponding":false},{"id":290767,"name":"Annie R. Piñeros","orcid":"0000-0003-0135-7549","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T00:23:05.485568Z","pmid":"35767947","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}