{"doi":"10.1016/j.celrep.2022.111255","title":"Macrophages and neutrophils are necessary for ER stress-induced β cell loss","abstract":"Persistent endoplasmic reticulum (ER) stress induces islet inflammation and β cell loss. How islet inflammation contributes to β cell loss remains uncertain. We have reported previously that chronic overnutrition-induced ER stress in β cells causes Ripk3-mediated islet inflammation, macrophage recruitment, and a reduction of β cell numbers in a zebrafish model. We show here that β cell loss results from the intricate communications among β cells, macrophages, and neutrophils. Macrophage-derived Tnfa induces cxcl8a in β cells. Cxcl8a, in turn, attracts neutrophils to macrophage-contacted \"hotspots\" where β cell loss occurs. We also show potentiation of chemokine expression in stressed mammalian β cells by macrophage-derived TNFA. In Akita and db/db mice, there is an increase in CXCL15-positive β cells and intra-islet neutrophils. Blocking neutrophil recruitment in Akita mice preserves β cell mass and slows diabetes progression. These results reveal an important role of neutrophils in persistent ER stress-induced β cell loss.","journal":"Cell Reports","year":2022,"id":244048,"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":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"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":877169,"name":"Liu Yang","orcid":"0000-0003-0705-5509","position":1,"is_corresponding":false},{"id":484216,"name":"Yueyang Wang","orcid":"0000-0002-5445-8186","position":2,"is_corresponding":false},{"id":345675,"name":"Lisette A. Maddison","orcid":"0000-0002-7725-9745","position":3,"is_corresponding":false},{"id":345678,"name":"Zihan Tang","orcid":"0000-0003-3769-0327","position":4,"is_corresponding":false},{"id":877878,"name":"Sander Haigh","orcid":null,"position":5,"is_corresponding":false},{"id":877170,"name":"Yulong Gong","orcid":"0000-0003-2241-8718","position":6,"is_corresponding":false},{"id":734003,"name":"Yue Zhang","orcid":"0000-0001-6682-0093","position":7,"is_corresponding":false},{"id":877171,"name":"Brittney A. Covington","orcid":"0000-0002-1254-3649","position":8,"is_corresponding":false},{"id":304324,"name":"Karin J. Bosma","orcid":"0000-0002-1221-1169","position":9,"is_corresponding":false},{"id":461847,"name":"Xin Tong","orcid":"0000-0003-4408-3832","position":10,"is_corresponding":false},{"id":877172,"name":"Patrick Page-McCaw","orcid":"0000-0002-4139-9770","position":11,"is_corresponding":false},{"id":304325,"name":"Maureen Gannon","orcid":"0000-0003-3287-8101","position":12,"is_corresponding":false},{"id":484220,"name":"Qing Deng","orcid":"0000-0002-9254-9951","position":13,"is_corresponding":false},{"id":325641,"name":"Wenbiao Chen","orcid":"0000-0002-0750-8275","position":14,"is_corresponding":false},{"id":345674,"name":"Bingyuan Yang","orcid":"0000-0002-8553-9392","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T00:23:25.718788Z","pmid":"36001973","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":[]}