Mast Cell-Derived Exosomes Induce Phenotypic and Functional Maturation of Dendritic Cells and Elicit Specific Immune Responses In Vivo

DOI PDF 5 Citations
  • Dimitris Skokos
    *Unité d’Immuno-Allergie, Institut Pasteur and
  • Hany Goubran Botros
    *Unité d’Immuno-Allergie, Institut Pasteur and
  • Christian Demeure
    *Unité d’Immuno-Allergie, Institut Pasteur and
  • Joelle Morin
    †Laboratoire d’Immunologie, Génétique et Traitement des Maladies Métaboliques et du Diabète, Institut National de la Santé et de la Recherche Médicale, Unité 561, Hopital Saint Vincent de Paul, Paris, France; and
  • Roger Peronet
    *Unité d’Immuno-Allergie, Institut Pasteur and
  • Gerd Birkenmeier
    ‡Institute of Biochemistry, University of Leipzig, Leipzig, Germany
  • Sarah Boudaly
    †Laboratoire d’Immunologie, Génétique et Traitement des Maladies Métaboliques et du Diabète, Institut National de la Santé et de la Recherche Médicale, Unité 561, Hopital Saint Vincent de Paul, Paris, France; and
  • Salaheddine Mécheri
    *Unité d’Immuno-Allergie, Institut Pasteur and

Description

<jats:title>Abstract</jats:title><jats:p>Mast cells (MCs) are considered major players in IgE-mediated allergic responses, but have also recently been recognized as active participants in innate as well as specific immune responses. Recent work provided evidence that MCs are able to activate B and T lymphocytes through the release of vesicles called exosomes. Here we demonstrate that exosomes, which are located in the endocytic pathway, harbor exogenous Ags that associate with other molecules endowed with immunomodulatory functions, including 60- and 70-kDa heat shock proteins. Administration to naive mice of Ag-containing exosomes in the absence of conventional adjuvants elicits specific Ab responses across the MHC II haplotype barrier. We demonstrate that MC-exosomes induce immature dendritic cells (DCs) to up-regulate MHC class II, CD80, CD86, and CD40 molecules and to acquire potent Ag-presenting capacity to T cells. Uptake and processing of Ag-associated exosomes by endogenous DCs were also demonstrated. Finally, exosome-associated heat shock proteins are critical for the acquisition by DCs of the Ag-presenting function. This work demonstrates a heretofore unrecognized collaborative interaction between MCs and DCs leading to the elicitation of specific immune responses.</jats:p>

Journal

  • The Journal of Immunology

    The Journal of Immunology 170 (6), 3037-3045, 2003-03-15

    The American Association of Immunologists

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