2026-06-14T03:47:10Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/104832024-09-27T09:55:33Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Sanchez-Diaz, Raquel
author
Blanco-Dominguez, Rafael
author
Lasarte, Sandra
author
Tsilingiri, Katerina
author
Martin-Gayo, Enrique
author
Linillos-Pradillo, Beatriz
author
de la Fuente, Hortensia
author
Sanchez-Madrid, Francisco
author
Nakagawa, Rinako
author
Toribio, Maria L
author
Martin, Pilar
funder
Ministerio de Economía y Competitividad (España)
funder
Comunidad de Madrid (España)
funder
Instituto de Salud Carlos III
funder
Centro de Investigación Biomedica en Red - CIBER
funder
Fundación La Marató TV3
funder
Unión Europea
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación ProCNIC
2020-06-17T14:42:16Z
2020-06-17T14:42:16Z
2017-05
Mol Cell Biol. 2017; 37(9):e00341-16
10.1128/MCB.00341-16
1098-5549
Molecular and cellular biology
28167605
http://hdl.handle.net/20.500.12105/10483
Thymus-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.
eng
Thymus-Derived Regulatory T Cell Development Is Regulated by C-Type Lectin-Mediated BIC/MicroRNA 155 Expression.
journal article
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ThymusDerivedRegulatoryTCell_2017.pdf
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ThymusDerivedRegulatoryTCell_2017_SupplMat.pdf
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ThymusDerivedRegulatoryTCell_2017.pdf.txt
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