Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Department of Dermatology, Duke University Medical Center, Durham, NC 27710, USA.
Science. 2018 Nov 9;362(6415). 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.
当过敏原进入血液循环并激活免疫球蛋白 E(IgE)致敏的肥大细胞(MC)时,就会引发过敏反应,导致预先储存的促炎介质全身性释放。由于 MC 位于血管外,它们如何感知循环中的过敏原仍然是一个难题。在这里,我们描述了一种 CD301b 血管周树突状细胞(DC)亚群的存在,它不断地从血液中取样并将抗原传递给相邻的 MC,MC 会强烈脱颗粒并引发过敏反应。DC 抗原传递涉及通过液泡蛋白分选 4(VPS4)产生的 0.5-1.0 微米大小的微泡(MV)上表面相关抗原的主动排出。DC 的抗原共享不仅限于 MC,因为相邻的 DC 也获得了携带抗原的 MV。DC 将携带抗原的 MV 分配到血管周空间中的各种免疫细胞的这种能力增强了对血液传播抗原的炎症和免疫反应。