Background: Psoriasis is a chronic inflammatory dermatosis with an unclear pathogenesis. Mast cells (MCs) can serve as a bridge between innate and adaptive immunity and are involved in the regulation of the inflammatory state and immune homeostasis in diseases. MCs constitutively express interleukin-33 receptor T1/ST2 (IL-33R). IL-33 is a potent MCs activator that is actively secreted by keratinocytes in psoriasis. However, the regulatory role of MCs in psoriasis remains uncertain. Therefore, we hypothesised that IL-33 could promote MC activation to regulate psoriasis development.
Methods: We performed experiments on wild-type (WT) and MC-deficient (Kit Wsh/Wsh) mice, established psoriasis-like mouse models using imiquimod (IMQ), and performed RNA sequencing and transcriptomic analysis of skin lesions. Exogenous administration was performed using recombinant IL-33. Validation and evaluation were performed using PSI scoring, immunofluorescence, immunohistochemistry, and qPCR.
Results: We observed an upregulation in the number and activation of MCs in patients with psoriasis and in IMQ-induced psoriasis-like dermatitis. Deficiency of MCs ameliorates IMQ-induced psoriatic dermatitis at an early stage. IL-33 is increased and co-localized with MCs in the dermis of psoriasis-like lesions using immunofluorescence. Compared to WT mice, IMQ-induced KitWsh/Wsh mice demonstrated a delayed response to exogenous IL-33.
Conclusions: MCs are activated by IL-33 in the early stages of psoriasis and exacerbate psoriasis-associated skin inflammation. The regulation of MC homeostasis may be a potential therapeutic strategy for psoriasis. Video Abstract.
© 2023. The Author(s).