Anaphylaxis is a severe allergic response characterized by the development of hives, swelling, and dramatic drops in blood pressure. It is estimated that 1,500 people in the United States die yearly from anaphylaxis. A plethora of substances can elicit allergic reactions, and the exact allergen is often unknown. What is known is that an allergen binds to IgE found on mast cells, and this leads to the release of inflammatory mediators such as histamine, the substances responsible for the allergic response. Mast cells are found in tissue, yet can respond to allergens in the blood via a mechanism that is not well understood.
Results of recent research suggest that mast cells may directly sample the blood to detect and acquire allergens. To determine how this is accomplished, a research team from the Duke University Research Center conducted a series of experiments, including one to identify the perivascular cells that acquire a labeled blood-bound antigen injected into mice. Dextran was the experimental antigen used because it cannot enter the extracellular space.
To detect the cells that acquired the labeled antigen, flow cytometry was performed on a mouse ear–derived skin cell suspension that was prepared 30 min after dextran injection. Although mast cells are the main players in the anaphylactic response, the majority of the antigen was acquired by a different cell type, dendritic cells. The specific subset identified is CD301b-expressing CD11c+ dermal dendritic cells that are found in the same vicinity of dermal abluminal mast cells. The dendrites of the dendritic cells can pass between endothelial cells and sample the luminal vessel blood.
In another arm of the study, the researchers used live confocal imaging to observe the uptake of labeled allergen by dendritic cells and their passage between dendritic cells and between dendritic and mast cells via microvesicles. The researchers found that dendritic cells are important mediators of anaphylaxis by injecting mice depleted of CD11c+ dendritic cells and performing passive systemic and passive cutaneous anaphylaxis assays.
Vascular leakage was observed in non-depleted mice but was significantly reduced in the depleted mice. This new insight into the role of dendritic cells in the mechanism of allergen response can provide the basis for the development of new and more effective allergy therapies.
Reference: Choi, H., Suwanpradid, J., Kim, I., Staats, H., Haniffa, M., MacLeod, A., & Abraham, S. (2018). Perivascular dendritic cells elicit anaphylaxis by relaying allergens to mast cells via microvesicles. Science, 362(6415), eaao0666. doi:10.1126/science.aao0666