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Perivascular Dendritic Cells Elicit Anaphylaxis by Relaying Allergens to Mast Cells Via Microvesicles

In work published online on November 9, 2018, in Science, Duke University Medical Center researchers, and colleagues, demonstrate that IgE-sensitized mast cells (MCs) (image) are indirectly activated by blood-borne allergens. In addition, the study revealshow perivascular dendritic cells (DCs) continuously sample blood and initiated and markedly enhance inflammatory and immune responses by rapidly discharging antigen-bearing microvesicles (MVs) to surrounding immune cells. the Science article is titled “Perivascular Dendritic Cells Elicit Anaphylaxis by Relaying Allergens to Mast Cells Via Microvesicles.” The results may resolve the conundrum of how mast cells, which are extravascular, are able to perceive and react to blood-borne allergens. The scientists describe the existence of a CD301b+ perivascular DC subset that continuously samples blood and relays antigens to neighboring MCs, which vigorously degranulate and trigger anaphylaxis. DC antigen transfer involved the active discharge of surface-associated antigens on 0.5- to 1.0-micrometer 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 antigen-bearing MVs to various immune cells in the perivascular space potentiates inflammatory and immune responses to blood-borne antigens. Anaphylaxis is a life-threatening allergic reaction triggered after antigen-specific immunoglobulin E (IgE) antibodies bind to target allergens. These antibodies than cross-link IgE-specific Fc receptors on the surface of MCs. The MCs rapidly release inflammatory mediators, including histamine, resulting in smooth muscle contraction, vasodilation, and blood vessel leakage. Because MCs are usually found in perivascular abluminal surface of blood vessels, it had been unclear, prior to the current work, how blood-borne allergens could interact with the MCs. The Duke scientists and colleagues used intravital imaging of the mouse vasculature to show that a special set of DCs sample blood-borne antigens and relay them to MCs on the surface of MVs. IgE-bound MCs then vigorously degranulate after contact with these MVs.

[Science abstract] [Science Perspectivs "Dangerous Liaisons in Anaphylaxis]