Dendritic cells derived exosomes migration to spleen and induction of inflammation are regulated by CCR7

Sci Rep. 2017 Feb 22:7:42996. doi: 10.1038/srep42996.

Abstract

Mature dendritic cells (DCs) home to secondary lymphoid organs through CC chemokine receptor 7 (CCR7). Exosomes derived from DCs (DC-exos) are reported to migrate to spleen and induce inflammation in vivo. In this study, we demonstrated that mature bone marrow DC-exos can activate immature DC and T cells in vitro. Then we intravenously injected DC-exos into C57BL/6 mice, observing that mature DC-exos accumulated more in spleen than immature DC-exos. These DC-exos in spleen could be uptaken by splenetic DCs and T cells and induce an inflammatory response. We further showed that the increased accumulation of mature DC-exos in spleen was regulated by CCR7, whose reduction led to a decrease of accumulation in spleen and attenuated inflammatory response in serum. These data provide us a new perspective to comprehensively understand exosomes, which might inherit some special functions from their parent cells and exert these functions in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cytokines / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism
  • Endocytosis
  • Exosomes / metabolism*
  • Exosomes / transplantation
  • Inflammation / etiology*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Optical Imaging
  • Organic Chemicals / chemistry
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Receptors, CCR7 / antagonists & inhibitors
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / metabolism*
  • Spleen / metabolism*

Substances

  • Ccr7 protein, mouse
  • Cytokines
  • Organic Chemicals
  • PKH67
  • RNA, Small Interfering
  • Receptors, CCR7