Fig. 5: Proposed mechanism of F13A1 and the coagulation pathway in IgE-binding monocytes to promote allergic inflammation in the skin.

IgE-binding monocytes (IgE+ Mono) circulate in peripheral blood. It is expected that these monocytes can home to the skin and we hypothesize that they help promote skin inflammation following allergen exposure in allergic individuals. A IgE-binding monocytes in peripheral blood of allergic individuals are triggered by increased levels of allergy-associated cytokines IL-4 and IL-13, likely from basophils. This upregulates F13A1. B IgE-binding monocytes, expressing F13A1, home to the skin. C In the skin, they are exposed to more IL-4 and IL-13 when mast cells degranulate following allergen exposure. F13A1 expression increases further. D IgE-binding monocytes, which will differentiate into macrophages or dendritic cells, upregulate the coagulation cascade and deposit excess fibrin and C1R, ultimately leading to scar tissue build-up and exacerbating allergic wounds while also potentially using complement to guard against any additional microbes that may enter the broken skin. E Meanwhile, in healthy individuals, IgE-binding monocytes are not exposed to IL-4 and IL-13, do not upregulate F13A1 or the coagulation cascade, and respond appropriately to allergen by not promoting skin inflammation. IgE-binding monocytes also upregulate CCR10, suggesting a mechanism for homing to healthy skin. F In addition, mast cells do not degranulate in tissues and homeostasis is maintained. Image was created on biorender.com.