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Immunological synapse formation inhibits, via NF-κB and FOXO1, the apoptosis of dendritic cells

Nature Immunology volume 10, pages 753–760 (2009)Cite this article

A Corrigendum to this article was published on 01 June 2010

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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-κB 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.

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Figure 1: DCs show a higher tendency to become apoptotic than CD4 T cells.
Figure 2: IS formation protects DCs from apoptosis in serum-free conditions.
Figure 3: IS formation protects DCs from apoptosis in lymph nodes.
Figure 4: IS(DC) is a signaling region where Akt1 is activated.
Figure 5: Akt1 facilitates apoptosis protection induced by IS(DC) formation.
Figure 6: IS(DC) formation induces translocation of NF-κB to the DC nucleus.
Figure 7: FOXO1 regulates DC survival.
Figure 8: IS(DC) formation induces nuclear translocation of FOXO1.
Figure 9: Stimulation of CD40 induces activation of Akt1.

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  • 11 February 2010

    In the version of this article initially published, a citation was omitted. It should be cited in the third paragraph of the Discussion section after the second sentence as follows: In this context, it has been suggested that Notch1, another receptor located at the IS(DC), may inhibit the apoptosis of DCs by inducing activation of Akt and STAT3, a transcription factor that promotes cell survival51. The bibliographic information is as follows: 51. Luty, W.H., Rodeberg, D., Parness, J. & Vyas, YM. Antiparallel segregation of notch components in the immunological synapse directs reciprocal signaling in allogeneic Th:DC conjugates. J. Immunol. 179, 819–829 (2007).

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Acknowledgements

We thank A.L. Corbí and V.S. Martínez for their support, G. de la Rosa for help in the initial stages of this project, C. Ardavín for OTII mice, J. Villarejo and I. Treviño for help in obtaining blood samples, R. Borstein for umbilical cords, J.A. Schmid (Medical University of Vienna) for the p65-GFP construct, T. Balla (US National Institutes of Health) for the PH (Akt)-GFP plasmid, T.G. Unterman for the FOXO1-GFP plasmid, N. Hogg (Cancer Research UK) for anti-LFA-1 α-subunit, P. Lastres for help with the cytometer, A. García-Sánz for discussions and C. Escribano-Díaz for critical reading of the manuscript. Supported by (Ministerio de Educación y Ciencia (BFI-2001-0228 and SAF2005-00801), RETICS Program/Instituto de Salud Carlos III (RIER) (RD08/0075 to J.L.R.-F.), Ministerio de Sanidad (scholarship associated with PI021058 to L.R.-B.) and the Ministerio de Educación y Ciencia of Spain (fellowships FPI to C.D.-M. and FPU to N.S.-S.).

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  1. Lorena Riol-Blanco

    Present address: Present address: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.,

Authors and Affiliations

  1. Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain

    Lorena Riol-Blanco, Cristina Delgado-Martín, Noelia Sánchez-Sánchez & José Luis Rodríguez-Fernández

  2. Centro de Microscopía y Citometría, Universidad Complutense, Madrid, Spain

    Luis M Alonso-C

  3. Centro de Biología Molecular Severo Ochoa, CSIC, Madrid, Spain

    María Dolores Gutiérrez-López & Carlos Cabañas

  4. Servicio de Inmunología, Hospital de La Princesa, Universidad Autónoma, Madrid, Spain

    Gloria Martínez del Hoyo & Francisco Sánchez-Madrid

  5. Laboratorio de Inmunooncología, Hospital Gregorio Marañón, Madrid, Spain

    Joaquín Navarro & Paloma Sánchez-Mateos

  6. Departamento de Biología Vascular e Inflamación, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain

    Francisco Sánchez-Madrid

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Contributions

L.R.-B., C.D.-M. and J.L.R.-F. designed research; L.R.-B., C.D.-M., N.S.-S., L.M.A.-C. and G.M.d.H. performed research; L.M.A.-C., M.D.G.-L., G.M.d.H., J.N., F.S.-M., P.S.-M. and C.C., provided analytical tools; L.R.-B., C.D.-M. and J.L.R.-F. analyzed data; J.L.R.-F. wrote the paper.

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Correspondence to José Luis Rodríguez-Fernández.

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Riol-Blanco, L., Delgado-Martín, C., Sánchez-Sánchez, N. et al. Immunological synapse formation inhibits, via NF-κB and FOXO1, the apoptosis of dendritic cells. Nat Immunol 10, 753–760 (2009). https://doi.org/10.1038/ni.1750

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