PMID- 30409859 OWN - NLM STAT- MEDLINE DCOM- 20190508 LR - 20200225 IS - 1095-9203 (Electronic) IS - 0036-8075 (Print) IS - 0036-8075 (Linking) VI - 362 IP - 6415 DP - 2018 Nov 9 TI - Perivascular dendritic cells elicit anaphylaxis by relaying allergens to mast cells via microvesicles. LID - 10.1126/science.aao0666 [doi] LID - eaao0666 AB - Anaphylactic reactions are triggered when allergens enter the blood circulation and activate immunoglobulin E (IgE)-sensitized mast cells (MCs), causing systemic discharge of prestored proinflammatory mediators. As MCs are extravascular, how they perceive circulating allergens remains a conundrum. Here, we describe the existence of a CD301b(+) perivascular dendritic cell (DC) subset that continuously samples blood and relays antigens to neighboring MCs, which vigorously degranulate and trigger anaphylaxis. DC antigen transfer involves the active discharge of surface-associated antigens on 0.5- to 1.0-micrometer microvesicles (MVs) generated by vacuolar protein sorting 4 (VPS4). Antigen sharing by DCs is not limited to MCs, as neighboring DCs also acquire antigen-bearing MVs. This capacity of DCs to distribute antigen-bearing MVs to various immune cells in the perivascular space potentiates inflammatory and immune responses to blood-borne antigens. CI - Copyright (c) 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. FAU - Choi, Hae Woong AU - Choi HW AUID- ORCID: 0000-0001-9372-1875 AD - Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. haewoong.choi@duke.edu. FAU - Suwanpradid, Jutamas AU - Suwanpradid J AD - Department of Dermatology, Duke University Medical Center, Durham, NC 27710, USA. FAU - Kim, Il Hwan AU - Kim IH AD - Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. FAU - Staats, Herman F AU - Staats HF AUID- ORCID: 0000-0003-1039-1087 AD - Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. AD - Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA. AD - Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA. FAU - Haniffa, Muzlifah AU - Haniffa M AUID- ORCID: 0000-0002-3927-2084 AD - Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. AD - Department of Dermatology, Newcastle upon Tyne NHS Trust, Newcastle upon Tyne NE1 4LP, UK. FAU - MacLeod, Amanda S AU - MacLeod AS AD - Department of Dermatology, Duke University Medical Center, Durham, NC 27710, USA. AD - Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA. FAU - Abraham, Soman N AU - Abraham SN AUID- ORCID: 0000-0002-1662-2096 AD - Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. AD - Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA. AD - Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA. AD - Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore 169857, Singapore. LA - eng GR - R01 AI096305/AI/NIAID NIH HHS/United States GR - R21 AI128727/AI/NIAID NIH HHS/United States GR - R56 DK095198/DK/NIDDK NIH HHS/United States GR - U01 AI082107/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Allergens) RN - 0 (Endosomal Sorting Complexes Required for Transport) RN - 0 (Lectins, C-Type) RN - 0 (MGL2 protein, mouse) RN - EC 3.6.4.- (ATPases Associated with Diverse Cellular Activities) RN - EC 3.6.4.6 (Vps4b protein, mouse) SB - IM CIN - Science. 2018 Nov 9;362(6415):640-641. PMID: 30409871 CIN - Immunity. 2018 Dec 18;49(6):999-1001. PMID: 30566890 MH - ATPases Associated with Diverse Cellular Activities/immunology MH - Allergens/*immunology MH - Anaphylaxis/*immunology MH - Animals MH - Blood Vessels/immunology MH - Cell-Derived Microparticles/*immunology MH - Dendritic Cells/*immunology MH - Endosomal Sorting Complexes Required for Transport/immunology MH - Female MH - Humans MH - Lectins, C-Type/immunology MH - Male MH - Mast Cells/*immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Mutant Strains MH - Primary Cell Culture MH - Skin/*immunology PMC - PMC6376486 MID - NIHMS1006357 EDAT- 2018/11/10 06:00 MHDA- 2019/05/09 06:00 PMCR- 2019/02/15 CRDT- 2018/11/10 06:00 PHST- 2017/06/10 00:00 [received] PHST- 2018/04/20 00:00 [revised] PHST- 2018/09/12 00:00 [accepted] PHST- 2018/11/10 06:00 [entrez] PHST- 2018/11/10 06:00 [pubmed] PHST- 2019/05/09 06:00 [medline] PHST- 2019/02/15 00:00 [pmc-release] AID - 362/6415/eaao0666 [pii] AID - 10.1126/science.aao0666 [doi] PST - ppublish SO - Science. 2018 Nov 9;362(6415):eaao0666. doi: 10.1126/science.aao0666.