Perivascular dendritic cells elicit anaphylaxis by relaying allergens to mast cells via microvesicles

Science. 2018 Nov 9;362(6415):eaao0666. doi: 10.1126/science.aao0666.


Anaphylactic reactions are triggered when allergens enter the blood circulation and activate immunoglobulin E (IgE)-sensitized mast cells (MCs), causing systemic discharge of prestored proinflammatory mediators. As MCs are extravascular, how they perceive circulating allergens remains a conundrum. Here, we describe the existence of a CD301b+ perivascular dendritic cell (DC) subset that continuously samples blood and relays antigens to neighboring MCs, which vigorously degranulate and trigger anaphylaxis. DC antigen transfer involves the active discharge of surface-associated antigens on 0.5- to 1.0-micrometer microvesicles (MVs) generated by vacuolar protein sorting 4 (VPS4). Antigen sharing by DCs is not limited to MCs, as neighboring DCs also acquire antigen-bearing MVs. This capacity of DCs to distribute antigen-bearing MVs to various immune cells in the perivascular space potentiates inflammatory and immune responses to blood-borne antigens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / immunology
  • Allergens / immunology*
  • Anaphylaxis / immunology*
  • Animals
  • Blood Vessels / immunology
  • Cell-Derived Microparticles / immunology*
  • Dendritic Cells / immunology*
  • Endosomal Sorting Complexes Required for Transport / immunology
  • Female
  • Humans
  • Lectins, C-Type / immunology
  • Male
  • Mast Cells / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Primary Cell Culture
  • Skin / immunology*


  • Allergens
  • Endosomal Sorting Complexes Required for Transport
  • Lectins, C-Type
  • MGL2 protein, mouse
  • ATPases Associated with Diverse Cellular Activities
  • Vps4b protein, mouse