PMID- 32195350 OWN - NLM STAT- MEDLINE DCOM- 20201112 LR - 20210919 IS - 2375-2548 (Electronic) IS - 2375-2548 (Linking) VI - 6 IP - 11 DP - 2020 Mar TI - Platelet P-selectin initiates cross-presentation and dendritic cell differentiation in blood monocytes. PG - eaaz1580 LID - 10.1126/sciadv.aaz1580 [doi] LID - eaaz1580 AB - Dendritic cells (DCs) are adept at cross-presentation and initiation of antigen-specific immunity. Clinically, however, DCs produced by in vitro differentiation of monocytes in the presence of exogenous cytokines have been met with limited success. We hypothesized that DCs produced in a physiological manner may be more effective and found that platelets activate a cross-presentation program in peripheral blood monocytes with rapid (18 hours) maturation into physiological DCs (phDCs). Differentiation of monocytes into phDCs was concomitant with the formation of an "adhesion synapse," a biophysical junction enriched with platelet P-selectin and monocyte P-selectin glycoprotein ligand 1, followed by intracellular calcium fluxing and nuclear localization of nuclear factor kappaB. phDCs were more efficient than cytokine-derived DCs in generating tumor-specific T cell immunity. Our findings demonstrate that platelets mediate a cytokine-independent, physiologic maturation of DC and suggest a novel strategy for DC-based immunotherapies. CI - Copyright (c) 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). FAU - Han, Patrick AU - Han P AUID- ORCID: 0000-0002-0370-0729 AD - Department of Chemical and Environmental Engineering, School of Engineering and Applied Science, Yale University, New Haven, CT 06511, USA. FAU - Hanlon, Douglas AU - Hanlon D AUID- ORCID: 0000-0003-4386-7491 AD - Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06511, USA. FAU - Arshad, Najla AU - Arshad N AUID- ORCID: 0000-0001-5553-311X AD - Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06511, USA. FAU - Lee, Jung Seok AU - Lee JS AD - Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University, New Haven, CT 06511, USA. FAU - Tatsuno, Kazuki AU - Tatsuno K AD - Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06511, USA. FAU - Robinson, Eve AU - Robinson E AD - Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06511, USA. FAU - Filler, Renata AU - Filler R AD - Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06511, USA. FAU - Sobolev, Olga AU - Sobolev O AD - Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06511, USA. FAU - Cote, Christine AU - Cote C AD - Yale Flow Cytometry Facility, School of Medicine, Yale University, New Haven, CT 06511, USA. FAU - Rivera-Molina, Felix AU - Rivera-Molina F AD - Yale CINEMA Lab, School of Medicine, Yale University, New Haven, CT 06511, USA. FAU - Toomre, Derek AU - Toomre D AD - Yale CINEMA Lab, School of Medicine, Yale University, New Haven, CT 06511, USA. FAU - Fahmy, Tarek AU - Fahmy T AUID- ORCID: 0000-0001-8740-4179 AD - Department of Chemical and Environmental Engineering, School of Engineering and Applied Science, Yale University, New Haven, CT 06511, USA. AD - Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06511, USA. AD - Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06511, USA. AD - Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University, New Haven, CT 06511, USA. FAU - Edelson, Richard AU - Edelson R AUID- ORCID: 0000-0002-1552-2480 AD - Department of Dermatology, School of Medicine, Yale University, New Haven, CT 06511, USA. LA - eng GR - R01 AI097206/AI/NIAID NIH HHS/United States GR - UL1 TR001863/TR/NCATS NIH HHS/United States GR - T32 AR007016/AR/NIAMS NIH HHS/United States GR - R01 GM118486/GM/NIGMS NIH HHS/United States GR - P30 DK045735/DK/NIDDK NIH HHS/United States GR - R21 AG026412/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20200311 PL - United States TA - Sci Adv JT - Science advances JID - 101653440 RN - 0 (Antigens, Neoplasm) RN - 0 (Membrane Glycoproteins) RN - 0 (NF-kappa B) RN - 0 (P-Selectin) RN - 0 (P-selectin ligand protein) SB - IM EIN - Sci Adv. 2021 Aug 27;7(35):. PMID: 34452922 MH - Animals MH - *Antigen Presentation MH - Antigens, Neoplasm/genetics/immunology MH - Blood Platelets/*immunology MH - Calcium Signaling/genetics/*immunology MH - Cell Differentiation/genetics/*immunology MH - Dendritic Cells/*immunology MH - Membrane Glycoproteins/genetics/immunology MH - Mice MH - Mice, Transgenic MH - Monocytes/*immunology MH - NF-kappa B/genetics/immunology MH - P-Selectin/genetics/*immunology MH - T-Lymphocytes/immunology PMC - PMC7065880 EDAT- 2020/03/21 06:00 MHDA- 2020/11/13 06:00 PMCR- 2020/03/11 CRDT- 2020/03/21 06:00 PHST- 2019/08/16 00:00 [received] PHST- 2019/12/17 00:00 [accepted] PHST- 2020/03/21 06:00 [entrez] PHST- 2020/03/21 06:00 [pubmed] PHST- 2020/11/13 06:00 [medline] PHST- 2020/03/11 00:00 [pmc-release] AID - aaz1580 [pii] AID - 10.1126/sciadv.aaz1580 [doi] PST - epublish SO - Sci Adv. 2020 Mar 11;6(11):eaaz1580. doi: 10.1126/sciadv.aaz1580. eCollection 2020 Mar.