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dc.contributor.author | Toribio-Fernandez, Raquel | |
dc.contributor.author | Herrero-Fernandez, Beatriz | |
dc.contributor.author | Zorita, Virginia | |
dc.contributor.author | Lopez, Juan Antonio | |
dc.contributor.author | Vazquez, Jesus | |
dc.contributor.author | Criado, Gabriel | |
dc.contributor.author | Pablos, Jose L | |
dc.contributor.author | Collas, Philippe | |
dc.contributor.author | Sanchez-Madrid, Francisco | |
dc.contributor.author | Andres, Vicente | |
dc.contributor.author | Gonzalez-Granado, Jose Maria | |
dc.date.accessioned | 2020-01-14T11:10:49Z | |
dc.date.available | 2020-01-14T11:10:49Z | |
dc.date.issued | 2019-12 | |
dc.identifier.citation | J Pathol. 2019; 249(4):509-22 | es_ES |
dc.identifier.issn | 0022-3417 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/8879 | |
dc.description.abstract | The mechanisms by which lamin A/C in CD4+ T-cells control intestinal homeostasis and can cause inflammatory bowel disease (IBD) are unknown. Here, we explore lamin A/C in a mouse model of IBD. Adoptive transfer to Rag1-/- mice of Lmna-/- CD4+ T-cells, which have enhanced regulatory T-cells (Treg) differentiation and function, induced less severe IBD than wild-type T-cells. Lamin A/C deficiency in CD4+ T-cells enhanced transcription of the Treg master regulator FOXP3, thus promoting Treg differentiation, and reduced Th1 polarization, due to epigenetic changes in the Th1 master regulator T-bet. In mesenteric lymph nodes, retinoic acid (RA) released by CD103+ dendritic cells downregulated lamin A/C in CD4+ T-cells, enhancing Treg differentiation. However, non-RA-producing CD103- dendritic cells predominated in peripheral lymph nodes, facilitating lamin A/C expression in CD4+ T-cells and therefore Th1 differentiation. Our findings establish lamin A/C as a key regulator of Th differentiation in physiological conditions and show it as a potential immune-regulatory target in IBD. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. | es_ES |
dc.description.sponsorship | This study was supported by grants to PC from the Research Council of Norway, to JMG-G from ISCIII (PI14/00526; PI17/01395; CP11/00145; CPII16/00022; EuroCellNet COST Action CA15214), the Miguel Servet Program and Fundación Ramón Aréces; to VA (RD12/0042/0028 SAF2013-46663-R, SAF2016-79490-R); to FS-M (SAF2017-82886-R; ERC-2011-AdG 294340-GENTRIS, CIBER CARDIOVASCULAR, PIE 13.0004-BIOIMID and CAM-B2017/BMD-3671-INFLAMUNE), to GC and JLP (PI16/00032 and RETICs RD16/0012 RIER), and to JV (BIO2015-67580-P; PRB3, IPT17/0019 - ISCIII-SGEFI/ERDF, ProteoRed) with co-funding from the European Regional Development Fund (ERDF) “Una manera de hacer Europa”. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). RTF is supported by the Fundación Ramón Aréces, VZG by ISCIII, BHF by the Instituto de Investigación Hospital 12 de Octubre (i+12), and JMG-G by the ISCIII Miguel Servet Program, i+12 and Universidad Autónoma de Madrid (UAM). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.type.hasVersion | AM | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | CD4+ T-cells | es_ES |
dc.subject | FOXP3 | es_ES |
dc.subject | Inflammatory bowel disease | es_ES |
dc.subject | Lamin A/C | es_ES |
dc.subject | Regulatory T-cell | es_ES |
dc.title | Lamin A/C deficiency in CD4+ T-cells enhances regulatory T-cells and prevents inflammatory bowel disease | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 31372995 | es_ES |
dc.format.volume | 249 | es_ES |
dc.format.number | 4 | es_ES |
dc.format.page | 509-522 | es_ES |
dc.identifier.doi | 10.1002/path.5332 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | The Research Council of Norway | |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | |
dc.contributor.funder | Unión Europea. European Cooperation in Science and Technology (COST) | |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | |
dc.contributor.funder | Centro de Investigación Biomedica en Red - CIBER | |
dc.contributor.funder | Fundación ProCNIC | |
dc.contributor.funder | Fundación Ramón Areces | |
dc.contributor.funder | Autonomous University of Madrid (España) | |
dc.contributor.funder | Research Institute Hospital 12 de Octubre | |
dc.description.peerreviewed | Sí | es_ES |
dc.embargo.terms | 2020-12-01 | es_ES |
dc.identifier.e-issn | 1096-9896 | es_ES |
dc.identifier.journal | The Journal of pathology | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genética | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Proteómica cardiovascular | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Comunicación Intercelular en la Respuesta Inflamatoria | es_ES |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Proteómica / Metabolómica | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/294340 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |
dc.rights.accessRights | open access | es_ES |