A physiological role for inducible FOXP3+ TREG cells: Lessons from women with reproductive failure

We have previously shown a decreased frequency and function of Tregs in women suffering from recurrent spontaneous abortions (RSA). In the current study, we first investigated the expression of FOXP3 after T-cell activation. We observed that expression of FOXP3 in activated PBMCs was already present...

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Detalles Bibliográficos
Autores: Arruvito, Maria Lourdes, Sotelo, Ana Isabel, Billordo, Luis Ariel, Fainboim, Leonardo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/18200
Acceso en línea:http://hdl.handle.net/11336/18200
Access Level:acceso abierto
Palabra clave:Inducible Treg Cells
Il-2
Stat-5
Human Reproduction
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descripción
Sumario:We have previously shown a decreased frequency and function of Tregs in women suffering from recurrent spontaneous abortions (RSA). In the current study, we first investigated the expression of FOXP3 after T-cell activation. We observed that expression of FOXP3 in activated PBMCs was already present above baseline before any cell division, indicating that it was induced in cells that were previously negative for this transcription factor. Because RSA women showed a more limited expansion of FOXP3-positive cells, we next assessed the role of IL-2 signaling through STAT5, which is known to be required for generation of inducible Tregs (iTregs). We demonstrated not only that TGF-β and IL-2 were diminished but also that the IL-2–STAT-5 signaling axis was down regulated in RSA women. Finally, in addition to a limited FOXP3+ cells expansion in vitro, iTregs from RSA women showed a strikingly lower suppressor activity.