Molecular Characterization of Dendritic Cell-derived Exosomes: Selective Accumulation of the Heat Shock Protein hsc73

Molecular Characterization of Dendritic Cell-derived Exosomes: Selective Accumulation of the Heat Shock Protein hsc73

Volume 147, Number 3, November 1, 1999 | Clotilde Théry, Armelle Regnault, Jérôme Garin, Joseph Wolfers, Laurence Zitvogel, Paola Ricciardi-Castagnoli, Graça Raposo, and Sebastian Amigorena
This study investigates the molecular characterization of dendritic cell (DC)-derived exosomes, which have been shown to induce potent antitumor immune responses in mice. The research focuses on the regulation of exosome production during DC maturation and the protein composition of these exosomes. Exosomes are found to accumulate a specific subset of cellular proteins, including cytosolic proteins (such as annexin II, hsc73, and Gi2α) and membrane proteins (such as MHC class II, Mac-1 integrin, CD9, and MFG-E8). MFG-E8, a major exosomal component, binds to integrins expressed by DCs and macrophages, suggesting its role in targeting exosomes to these professional antigen-presenting cells. Hsc73, another exosomal component, is a heat shock protein that induces antitumor immune responses in vivo, indicating its potential involvement in the exosome's antitumor effects. The production of exosomes is downregulated upon DC maturation, suggesting that they are primarily produced by immature DCs in peripheral tissues. The study provides insights into the biogenesis, targeting, and biological functions of DC-derived exosomes, highlighting their role in immune stimulation and tumor rejection.This study investigates the molecular characterization of dendritic cell (DC)-derived exosomes, which have been shown to induce potent antitumor immune responses in mice. The research focuses on the regulation of exosome production during DC maturation and the protein composition of these exosomes. Exosomes are found to accumulate a specific subset of cellular proteins, including cytosolic proteins (such as annexin II, hsc73, and Gi2α) and membrane proteins (such as MHC class II, Mac-1 integrin, CD9, and MFG-E8). MFG-E8, a major exosomal component, binds to integrins expressed by DCs and macrophages, suggesting its role in targeting exosomes to these professional antigen-presenting cells. Hsc73, another exosomal component, is a heat shock protein that induces antitumor immune responses in vivo, indicating its potential involvement in the exosome's antitumor effects. The production of exosomes is downregulated upon DC maturation, suggesting that they are primarily produced by immature DCs in peripheral tissues. The study provides insights into the biogenesis, targeting, and biological functions of DC-derived exosomes, highlighting their role in immune stimulation and tumor rejection.
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