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Publication : IL-33-mediated activation of mast cells is involved in the progression of imiquimod-induced psoriasis-like dermatitis.

First Author  Zhou X Year  2023
Journal  Cell Commun Signal Volume  21
Issue  1 Pages  52
PubMed ID  36894987 Mgi Jnum  J:335013
Mgi Id  MGI:7443326 Doi  10.1186/s12964-023-01075-7
Citation  Zhou X, et al. (2023) IL-33-mediated activation of mast cells is involved in the progression of imiquimod-induced psoriasis-like dermatitis. Cell Commun Signal 21(1):52
abstractText  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 Kit(Wsh/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.
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