dc.contributor.author | Céspedes, Pablo F | |
dc.contributor.author | Jainarayanan, Ashwin | |
dc.contributor.author | Fernández-Messina, Lola | |
dc.contributor.author | Valvo, Salvatore | |
dc.contributor.author | Saliba, David G | |
dc.contributor.author | Kurz, Elke | |
dc.contributor.author | Kvalvaag, Audun | |
dc.contributor.author | Chen, Lina | |
dc.contributor.author | Ganskow, Charity | |
dc.contributor.author | Colin-York, Huw | |
dc.contributor.author | Fritzsche, Marco | |
dc.contributor.author | Peng, Yanchun | |
dc.contributor.author | Dong, Tao | |
dc.contributor.author | Johnson, Errin | |
dc.contributor.author | Siller-Farfán, Jesús A | |
dc.contributor.author | Dushek, Omer | |
dc.contributor.author | Sezgin, Erdinc | |
dc.contributor.author | Peacock, Ben | |
dc.contributor.author | Law, Alice | |
dc.contributor.author | Aubert, Dimitri | |
dc.contributor.author | Engledow, Simon | |
dc.contributor.author | Attar, Moustafa | |
dc.contributor.author | Hester, Svenja | |
dc.contributor.author | Fischer, Roman | |
dc.contributor.author | Sánchez-Madrid, Francisco | |
dc.contributor.author | Dustin, Michael L | |
dc.date.accessioned | 2023-04-03T13:07:48Z | |
dc.date.available | 2023-04-03T13:07:48Z | |
dc.date.issued | 2022-06-16 | |
dc.identifier.citation | Nat Commun. 2022 Jun 16;13(1):3460 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/15740 | |
dc.description.abstract | The immunological synapse is a molecular hub that facilitates the delivery of three activation signals, namely antigen, costimulation/corepression and cytokines, from antigen-presenting cells (APC) to T cells. T cells release a fourth class of signaling entities, trans-synaptic vesicles (tSV), to mediate bidirectional communication. Here we present bead-supported lipid bilayers (BSLB) as versatile synthetic APCs to capture, characterize and advance the understanding of tSV biogenesis. Specifically, the integration of juxtacrine signals, such as CD40 and antigen, results in the adaptive tailoring and release of tSV, which differ in size, yields and immune receptor cargo compared with steadily released extracellular vesicles (EVs). Focusing on CD40L+ tSV as model effectors, we show that PD-L1 trans-presentation together with TSG101, ADAM10 and CD81 are key in determining CD40L vesicular release. Lastly, we find greater RNA-binding protein and microRNA content in tSV compared with EVs, supporting the specialized role of tSV as intercellular messengers. | es_ES |
dc.description.sponsorship | This work was funded by Wellcome Trust Principal Research Fellowship 100262Z/12/Z, the ERC Advanced Grant (SYNECT AdG
670930), and the Kennedy Trust for Rheumatology Research (KTRR) (all three to
M.L.D.). P.F.C.D was supported by EMBO Long-Term Fellowship (ALTF 1420–2015, in
conjunction with the European Commission (LTFCOFUND2013, GA-2013-609409) and
Marie Sklodowska-Curie Actions) and Oxford-Bristol Myers Squibb Fellowship. A.K.
was supported by H2020 and the Research Council of Norway (in conjunction with
Marie Sklodowska-Curie Actions 275466; to A.K.). M.F. and H.C.Y. thank the Wellcome
Trust (212343/Z/18/Z) and EPSRC (EP/S004459/1). The eTIRF-SIM platform was builtin collaboration with Micron (www.micronoxford.com), an Oxford-wide advanced
microscopy technology consortium supported by Wellcome Strategic Awards (091911
and 107457), and with additional funds from an MRC/EPSRC/BBSRC next-generation
imaging award and the Kennedy Trust for Rheumatology Research through the Kennedy
Institute Cell Dynamics Platform. We acknowledge the generous support of the Kennedy
Trust for Rheumatology Research, IDRM, and Carl Zeiss GMBH for the Airyscan LSM
980 confocal microscope used in this research. Y.P., T.D., and R.F. were supported by the
Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences
(CIFMS), China (grant number: 2018-I2M-2-002) and UK Medical Research Council
(MRC); E.S. was supported by Newton-Katip Celebi Institutional Links grant
(352333122) and SciLifeLab fellowship (to E.S.). F.S-M. was supported by grants
SAF2017-82886-R from the Spanish Ministry of Economy and Competitiveness
(MINECO), and “La Caixa” Banking Foundation (HR17-00016). We thank the NIH
Tetramer Core Facility for the synthesis of the HLA-DRB1*09:01 monomers used in this
study. We thank the Oxford Genomics Centre at the Wellcome Centre for Human
Genetics (funded by Wellcome Trust grant reference 203141/Z/16/Z) for the generation
and initial processing of the sequencing data. Finally, we thank the MS laboratory at the
Target Discovery Institute NDM (Oxford) led by Benedikt M. Kessler. Pablo F. Céspedes
is also known as Pablo F. Céspedes-Donoso (https://orcid.org/0000-0002-1641-4107). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | CD40 Ligand | es_ES |
dc.subject.mesh | Extracellular Vesicles | es_ES |
dc.subject.mesh | Immunological Synapses | es_ES |
dc.subject.mesh | Synaptic Vesicles | es_ES |
dc.subject.mesh | T-Lymphocytes | es_ES |
dc.title | T-cell trans-synaptic vesicles are distinct and carry greater effector content than constitutive extracellular vesicles. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 35710644 | es_ES |
dc.format.volume | 13 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 3460 | es_ES |
dc.identifier.doi | 10.1038/s41467-022-31160-3 | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | es_ES |
dc.contributor.funder | European Molecular Biology Organization | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea | es_ES |
dc.contributor.funder | The Research Council of Norway | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2041-1723 | es_ES |
dc.relation.publisherversion | 10.1038/s41467-022-31160-3 | es_ES |
dc.identifier.journal | Nature communications | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Comunicación Intercelular en la Respuesta Inflamatoria | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/ERC/670930 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/LTFCOFUND2013 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/GA-2013-609409 | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/HR17-00016 | es_ES |