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Les cellules dendritiques inflammatoires humaines utilisent une voie non-cytosolique pour la présentation croisée

Abstract : The presentation of exogenous antigens on MHC class I molecules, termed cross-presentation, is essential for the induction of cytotoxic CD8+ T cells. In mouse, dendritic cells (DC) that arise from monocytes (mo-DC) during inflammation play a key role in cytotoxic T cell responses by cross- presenting antigens directly in peripheral tissues. Whether human naturally-occuring mo- DC can cross-present is unknown. To address this question, we have used human mo-DC directly purified from peritoneal tumor ascites. Using single-cell RNA-seq, we first confirm that ascites DC contain exclusively monocyte-derived cells. Both ascites mo-DC and macrophages cross- present efficiently, but are unable to transfer exogenous proteins into their cytosol. Inhibition of cysteine proteases, but not of proteasome, abolishes cross-presentation by mo-DC. We conclude that human monocyte- derived cells cross-present exclusively using a vacuolar pathway. Finally, we demonstrate that only ascites mo-DC, but not macrophages, efficiently induce effector cytotoxic CD8+ T cells. These results will have important implications for harnessing cross-presentation for therapeutic purposes.
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Tsing-Lee Tang-Huau. Les cellules dendritiques inflammatoires humaines utilisent une voie non-cytosolique pour la présentation croisée. Immunologie. Université Sorbonne Paris Cité, 2018. Français. ⟨NNT : 2018USPCB001⟩. ⟨tel-02468363⟩

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