{"doi":"10.2337/db23-0770","title":"Selective Reduction of Ca2+-Independent Phospholipase A2β (iPLA2β)-Derived Lipid Signaling From Macrophages Mitigates Type 1 Diabetes Development","abstract":"Type 1 diabetes (T1D) is a consequence of autoimmune destruction of β-cells, and macrophages (MΦs) have a central role in initiating processes that lead to β-cell demise. We reported that Ca2+-independent phospholipase A2β (iPLA2β)-derived lipid (iDL) signaling contributes to β-cell death. Because MΦs express iPLA2β, we assessed its role in T1D development. We find that selective reduction of myeloid-iPLA2β in spontaneously diabetes-prone NOD mice 1) decreases proinflammatory eicosanoid production by MΦs, 2) favors the anti-inflammatory (M2-like) MΦ phenotype, and 3) diminishes activated CD4+ and CD8+ T-cells phenotype in the pancreatic infiltrate, prior to T1D onset. These outcomes are associated with a significant reduction in T1D. Further, inhibition of select proinflammatory lipid signaling pathways reduces M1-like MΦ polarization and adoptive transfer of M2-like MΦs reduces NOD T1D incidence, suggesting a mechanism by which iDLs impact T1D development. These findings identify MΦ-iPLA2β as a critical contributor to T1D development and potential target to counter T1D onset.","journal":"Diabetes","year":2024,"id":474073,"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":1,"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":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":803750,"name":"Tayleur D. White","orcid":null,"position":1,"is_corresponding":false},{"id":489004,"name":"Daniel Stephenson","orcid":"0000-0002-5698-3400","position":2,"is_corresponding":false},{"id":1262643,"name":"Benjamin Stephenson","orcid":null,"position":3,"is_corresponding":false},{"id":1310667,"name":"Ying Gai-Tusing","orcid":null,"position":4,"is_corresponding":false},{"id":315357,"name":"Paran Goel","orcid":"0009-0000-6494-632X","position":5,"is_corresponding":false},{"id":1310668,"name":"Daniel W. Phillips","orcid":null,"position":6,"is_corresponding":false},{"id":339192,"name":"Robert S. Welner","orcid":"0000-0003-2498-9469","position":7,"is_corresponding":false},{"id":427976,"name":"Xiaoyong Lei","orcid":"0000-0001-9113-452X","position":8,"is_corresponding":false},{"id":242185,"name":"Bruce D. Hammock","orcid":"0000-0003-1408-8317","position":9,"is_corresponding":false},{"id":489008,"name":"Charles E. Chalfant","orcid":"0000-0002-5844-5235","position":10,"is_corresponding":false},{"id":427977,"name":"Sasanka Ramanadham","orcid":"0000-0002-1664-0657","position":11,"is_corresponding":false},{"id":802921,"name":"Abdulaziz Almutairi","orcid":"0000-0002-2517-335X","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:06:09.108857Z","pmid":"39283670","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":[]}