Cell Communication and Signaling (Mar 2023)

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

  • Xuyue Zhou,
  • Yu Hu,
  • Lingxi Liu,
  • Lihao Liu,
  • Hongying Chen,
  • Dan Huang,
  • Mei Ju,
  • Chao Luan,
  • Kun Chen,
  • Jiaan Zhang

DOI
https://doi.org/10.1186/s12964-023-01075-7
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 12

Abstract

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Abstract 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