Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing, China.
Cell Commun Signal. 2023 Mar 9;21(1):52. doi: 10.1186/s12964-023-01075-7.
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.
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.
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 mice demonstrated a delayed response to exogenous IL-33.
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.
银屑病是一种病因不明的慢性炎症性皮肤病。肥大细胞（MCs）可以作为先天免疫和适应性免疫之间的桥梁，参与疾病中炎症状态和免疫稳态的调节。MCs 持续表达白细胞介素-33 受体 T1/ST2（IL-33R）。IL-33 是一种有效的 MCs 激活物，在银屑病中角质形成细胞中被积极分泌。然而，MCs 在银屑病中的调节作用仍不确定。因此，我们假设 IL-33 可以促进 MC 激活，从而调节银屑病的发展。
我们在野生型（WT）和 MC 缺陷（Kit Wsh/Wsh）小鼠中进行了实验，使用咪喹莫特（IMQ）建立了银屑病样小鼠模型，并对皮肤损伤进行了 RNA 测序和转录组分析。使用重组 IL-33 进行了外源给药。使用 PSI 评分、免疫荧光、免疫组织化学和 qPCR 进行了验证和评估。
我们观察到银屑病患者和 IMQ 诱导的银屑病样皮炎中 MC 数量和激活增加。MC 缺陷在早期改善了 IMQ 诱导的银屑病样皮炎。免疫荧光显示，IL-33 在银屑病样病变的真皮中增加并与 MC 共定位。与 WT 小鼠相比，IMQ 诱导的 Kit 小鼠对外源 IL-33 的反应延迟。
IL-33 在银屑病的早期阶段激活 MCs，并加剧与银屑病相关的皮肤炎症。调节 MC 动态平衡可能是银屑病的一种潜在治疗策略。
