{"doi":"10.1084/jem.20250887","title":"Splenic cDC1 efferocytosis and cross-presentation to CD8 T cells are promoted by GPR34 and lysophosphatidylserine","abstract":"Spleen conventional dendritic cells type 1 (cDC1) take up apoptotic cells (AC) and cross-present associated antigens to CD8 T cells. The receptors promoting AC uptake are incompletely defined. Here, we tested the function of GPR34, a receptor that responds to the phosphatidylserine (PS) catabolite lysoPS. GPR34 deficiency led to reduced AC uptake by cDC1 but not cDC2 or macrophages. Uptake of soluble antigen or heat-killed bacteria was unaffected, whereas uptake of eryptotic RBCs was reduced. Using AC harboring OVA, activation and proliferation of OT-I T cells were compromised in GPR34-deficient mice. Reciprocally, GPR34 overexpression led to enhanced AC uptake and OT-I proliferation. The enzymes PLA1A and ABHD16A have been implicated in generating lysoPS that can act on GPR34. PLA1A but not ABHD16A deficiency was associated with a reduced OT-I response to AC-associated OVA. In conclusion, we identify a receptor requirement for cDC1 efferocytosis and cross-presentation and suggest a model where PLA1A catabolizes PS on AC to generate GPR34 ligands.","journal":"The Journal of Experimental Medicine","year":2025,"id":535347,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":841809,"name":"Haolin Shen","orcid":"0000-0003-1550-2831","position":1,"is_corresponding":false},{"id":1268733,"name":"Ying Xu","orcid":"0009-0002-8618-1561","position":2,"is_corresponding":false},{"id":385609,"name":"Jinping An","orcid":"0009-0009-5158-4505","position":3,"is_corresponding":false},{"id":235419,"name":"Jason G. Cyster","orcid":"0000-0002-4735-9745","position":4,"is_corresponding":false},{"id":1049553,"name":"H.K. Tam","orcid":"0000-0001-5772-0680","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T02:51:56.297114Z","pmid":"41212150","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":[]}