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dc.contributor.authorSanchez-Diaz, Raquel 
dc.contributor.authorBlanco-Dominguez, Rafael
dc.contributor.authorLasarte, Sandra
dc.contributor.authorTsilingiri, Katerina 
dc.contributor.authorMartin-Gayo, Enrique
dc.contributor.authorLinillos-Pradillo, Beatriz
dc.contributor.authorde la Fuente, Hortensia 
dc.contributor.authorSanchez-Madrid, Francisco 
dc.contributor.authorNakagawa, Rinako
dc.contributor.authorToribio, Maria L
dc.contributor.authorMartin, Pilar
dc.identifier.citationMol Cell Biol. 2017; 37(9):e00341-16es_ES
dc.description.abstractThymus-derived regulatory T (tTreg) cells are key to preventing autoimmune diseases, but the mechanisms involved in their development remain unsolved. Here, we show that the C-type lectin receptor CD69 controls tTreg cell development and peripheral Treg cell homeostasis through the regulation of BIC/microRNA 155 (miR-155) and its target, suppressor of cytokine signaling 1 (SOCS-1). Using Foxp3-mRFP/cd69+/- or Foxp3-mRFP/cd69-/- reporter mice and short hairpin RNA (shRNA)-mediated silencing and miR-155 transfection approaches, we found that CD69 deficiency impaired the signal transducer and activator of transcription 5 (STAT5) pathway in Foxp3+ cells. This results in BIC/miR-155 inhibition, increased SOCS-1 expression, and severely impaired tTreg cell development in embryos, adults, and Rag2-/- γc-/- hematopoietic chimeras reconstituted with cd69-/- stem cells. Accordingly, mirn155-/- mice have an impaired development of CD69+ tTreg cells and overexpression of the miR-155-induced CD69 pathway, suggesting that both molecules might be concomitantly activated in a positive-feedback loop. Moreover, in vitro-inducible CD25+ Treg (iTreg) cell development is inhibited in Il2rγ-/-/cd69-/- mice. Our data highlight the contribution of CD69 as a nonredundant key regulator of BIC/miR-155-dependent Treg cell development and homeostasis.es_ES
dc.description.sponsorshipThis study was funded by a grant from the Spanish Ministry of Economy and Competitiveness (SAF2013-44857-R to M.L.T.), grant INDISNET 01592006 from the Comunidad de Madrid to P.M. and F.S.-M., and grants from the Instituto de Salud Carlos III (PI-FIS-2016-9488 to P.M.), the CIBER de Enfermedades Cardiovasculares to F.S.-M. and P.M., and the Fundacio La Marato TV3 (20152330 31) to P.M. and F.S.-M. R.S.-D. was funded by a predoctoral fellowship from the Comunidad de Madrid, S.L. was funded by a contract from the RETICS Enfermedades Cardiovasculares (Instituto de Salud Carlos III), and K.T. is cofunded by the European Union Marie Curie Program (COFUND CNIC IPP). This research has been cofinanced by FEDER. The CNIC is supported by the Ministry of Economy, Industry, and Competitiveness (MINECO) and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505).es_ES
dc.publisherAmerican Society for Microbiology (ASM) es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAntigens, CD es_ES
dc.subject.meshAntigens, Differentiation, T-Lymphocyte es_ES
dc.subject.meshCell Differentiation es_ES
dc.subject.meshCells, Cultured es_ES
dc.subject.meshChimera es_ES
dc.subject.meshLectins, C-Type es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Inbred C57BL es_ES
dc.subject.meshMice, Knockout es_ES
dc.subject.meshMicroRNAs es_ES
dc.subject.meshOrgan Culture Techniques es_ES
dc.subject.meshRNA Interference es_ES
dc.subject.meshRNA, Small Interfering es_ES
dc.subject.meshSTAT5 Transcription Factor es_ES
dc.subject.meshSuppressor of Cytokine Signaling 1 Protein es_ES
dc.subject.meshT-Lymphocytes, Regulatory es_ES
dc.subject.meshThymus Gland es_ES
dc.titleThymus-Derived Regulatory T Cell Development Is Regulated by C-Type Lectin-Mediated BIC/MicroRNA 155 Expression.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderComunidad de Madrid (España) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderCentro de Investigación Biomedica en Red - CIBER
dc.contributor.funderFundación La Marató TV3 
dc.contributor.funderUnión Europea 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderFundación ProCNIC 
dc.identifier.journalMolecular and cellular biologyes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Moléculas Reguladoras de los Procesos Inflamatorioses_ES
dc.rights.accessRightsopen accesses_ES

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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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