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Life Sci Alliance. 2018 Dec 3;1(6):e201800093. doi: 10.26508/lsa.201800093. eCollection 2018 Dec.

Extracellular vesicles from mature dendritic cells (DC) differentiate monocytes into immature DC.

Author information

1
Department of Dermatology, University Hospital Erlangen, Kussmaul Campus, Erlangen, Germany.
2
Department of Immune Modulation, University Hospital Erlangen, Kussmaul Campus, Erlangen, Germany.
3
TissueGnostics GmbH, Wien, Austria.
4
Institute of Virology and Immunobiology, Würzburg, Germany.

Abstract

During inflammation, murine and human monocytes can develop into dendritic cells (DC), but this process is not entirely understood. Here, we demonstrate that extracellular vesicles (EV) secreted by mature human DC (maDC) differentiate peripheral monocytes into immature DC, expressing a unique marker pattern, including 6-sulfo LacNAc (slan), Zbtb46, CD64, and CD14. While EV from both maDC and immature DC differentiated monocytes similar to GM-CSF/IL-4 stimulation, only maDC-EV produced precursors, which upon maturation stimulus developed into T-cell-activating and IL-12p70-secreting maDC. Mechanistically, maDC-EV induced cell signaling through GM-CSF, which was abundant in EV as were IL-4 and other cytokines and chemokines. When injected into the mouse skin, murine maDC-EV attracted immune cells including monocytes that developed activation markers typical for inflammatory cells. Skin-injected EV also reached lymph nodes, causing a similar immune cell infiltration. We conclude that DC-derived EV likely serve to perpetuate an immune reaction and may contribute to chronic inflammation.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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