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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.<\/jats:p>","DOI":"10.1084\/jem.20250887","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T14:30:48Z","timestamp":1762785048000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Splenic cDC1 efferocytosis and cross-presentation to CD8 T cells are promoted by GPR34 and lysophosphatidylserine"],"prefix":"10.1084","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5772-0680","authenticated-orcid":true,"given":"Hanson","family":"Tam","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}],"name":"Howard Hughes Medical Institute, University of California, San Francisco 1 , San Francisco, CA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California, San Francisco 2 Department of Microbiology and Immunology, , San Francisco, CA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Scientist Training Program, University of California, San Francisco 3 , San Francisco, CA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Biomedical Sciences Graduate Program, University of California, San Francisco 4 , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1550-2831","authenticated-orcid":true,"given":"Haolin","family":"Shen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}],"name":"Howard Hughes Medical Institute, University of California, San Francisco 1 , San Francisco, CA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California, San Francisco 2 Department of Microbiology and Immunology, , San Francisco, CA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Biomedical Sciences Graduate Program, University of California, San Francisco 4 , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8618-1561","authenticated-orcid":true,"given":"Ying","family":"Xu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}],"name":"Howard Hughes Medical Institute, University of California, San Francisco 1 , San Francisco, CA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California, San Francisco 2 Department of Microbiology and Immunology, , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5158-4505","authenticated-orcid":true,"given":"Jinping","family":"An","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}],"name":"Howard Hughes Medical Institute, University of California, San Francisco 1 , San Francisco, CA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California, San Francisco 2 Department of Microbiology and Immunology, , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4735-9745","authenticated-orcid":true,"given":"Jason G.","family":"Cyster","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}],"name":"Howard Hughes Medical Institute, University of California, San Francisco 1 , San Francisco, CA,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California, San Francisco 2 Department of Microbiology and Immunology, , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"2025111009304003800_bib1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1084\/jem.20142350","article-title":"XCR1+ dendritic cells promote memory CD8+ T cell recall upon secondary infections with Listeria monocytogenes or certain viruses","volume":"213","author":"Alexandre","year":"2016","journal-title":"J. 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