Abstract
Background: Imiquimod (IMQ) is a common drug in skin disease therapy. However, the side effects of IMQ occurred frequently, which manifested as erythema, itchy dermatitis, and the mechanism has not been fully understood. Mast cells have been found in the lesion after IMQ treatment, and MRGPRX2 on mast cells has been proved to induce pseudo-allergic reaction in chronic urticaria, contact dermatitis, and other skin diseases. Whether IMQ related dermatitis is mediated by mast cell degranulation via MrpgrB2/MRGPRX2 need to be addressed.
Objectives: To investigate whether IMQ could activate mast cell degranulation via MrgprB2/MRGPRX2 in IMQ related dermatitis.
Methods: IMQ was applied on skin of mouse for three consecutive days to establish the IMQ dermatitis mouse model. H&E staining were obtained to observe changes of histopathology while immunofluorescence was used to evaluate the degranulation of mast cells in lesions of IMQ related dermatitis. Mice hindpaw swelling, enzyme-linked immunosorbent assays, and degranulation assays were performed to measure allergic mediators both in vivo and in vitro.
Results: IMQ induced dermatitis, paw swelling through activating mast cells degranulation and increased levels of cytokines and histamine in the serum of wild type mice, but did not increase in IgE level. In contrast, local allergic reactions were reduced or impaired in kitW-sh/W-sh and MrgprB2-knockout mice. Meanwhile, treatment with IMQ in MrgprB2-HEK293 cells showed dose-dependent increases in intracellular Ca2+ concentration, but not effectively trigger the calcium flux in NC-HEK293 cells. Further, IMQ increased the release rate of β-hexosaminidase in LAD2 cells but not in MRGPRX2 knock-down LAD2 cells. 
Conclusions: IMQ related dermatitis may be mediated by MrgprB2/MRGPRX2 on mast cells, which lays a foundation for the possible prevention of side effects.

Mas-related G-protein coupled receptor-B2 participates in imiquimod induced dermatitis through degranulation of mast cell