Article abstract
Nature Immunology 10, 753 - 760 (2009)
Published online: 7 June 2009 | doi:10.1038/ni.1750
Immunological synapse formation inhibits, via NF-
B and FOXO1, the apoptosis of dendritic cells
Lorena Riol-Blanco1,7, Cristina Delgado-Martín1, Noelia Sánchez-Sánchez1, Luis M Alonso-C2, María Dolores Gutiérrez-López3, Gloria Martínez del Hoyo4, Joaquín Navarro5, Francisco Sánchez-Madrid4,6, Carlos Cabañas3, Paloma Sánchez-Mateos5 & José Luis Rodríguez-Fernández1
Abstract
The immunological synapse (IS) is a cell–cell junction formed between CD4+ T cells and dendritic cells (DCs). Here we show in vitro and in vivo that IS formation inhibits apoptosis of DCs. Consistent with these results, IS formation induced antiapoptotic signaling events, including activation of the kinase Akt1 and localization of the prosurvival transcription factor NF-
B and the proapoptotic transcription factor FOXO1 to the nucleus and cytoplasm, respectively. Inhibition of phosphatidylinositol 3-OH kinase and Akt1 partially prevented the antiapoptotic effects of IS formation. Direct stimulation of the IS component CD40 on DCs leads to the activation of Akt1, suggesting the involvement of this receptor in the antiapoptotic effects observed upon IS formation.
- Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
- Centro de Microscopía y Citometría, Universidad Complutense, Madrid, Spain.
- Centro de Biología Molecular Severo Ochoa, CSIC, Madrid, Spain.
- Servicio de Inmunología, Hospital de La Princesa, Universidad Autónoma, Madrid, Spain.
- Laboratorio de Inmunooncología, Hospital Gregorio Marañón, Madrid, Spain.
- Departamento de Biología Vascular e Inflamación, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
- Present address: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Correspondence to: José Luis Rodríguez-Fernández1 e-mail: rodrifer@cib.csic.es
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