Glasgow Biomedical Research Centre, University of Glasgow, UK.
Eur J Immunol. 2011 Aug;41(8):2229-37. doi: 10.1002/eji.201041360. Epub 2011 Jun 24.
Psoriasis is a common chronic autoimmune condition of the skin characterized by hyperplasia of epidermal keratinocytes associated with pro-inflammatory cytokines. IL-33 is a new member of the IL-1 superfamily that signals through the ST2 receptor and was originally defined as an inducer of T helper 2 (Th2) cytokines. Recently, broader immune activatory potential has been defined for IL-33 particularly via mast cell activation and neutrophil migration. Here, we show that ST2(-/-) mice exhibit reduced cutaneous inflammatory responses compared with WT mice in a phorbol ester-induced model of skin inflammation. Furthermore, injections of IL-33 into the ears of mice induce an inflammatory skin lesion. This inflammatory response was partially dependent on mast cells as mast cell-deficient mice (Kit(W-sh/W-sh) ) showed delayed responses to IL-33. IL-33 also recruited neutrophils to the ear, an effect mediated in part by increased production of the chemokine KC (CXCL1). Finally, we show that IL-33 expression is up-regulated in the epidermis of clinical psoriatic lesions, compared with healthy skin. These results therefore demonstrate that IL-33 may play a role in psoriasis-like plaque inflammation. IL-33 targeting may provide a new treatment strategy for psoriasis.
银屑病是一种常见的慢性自身免疫性皮肤病，其特征是表皮角质形成细胞增生，伴有促炎细胞因子。IL-33 是 IL-1 超家族的新成员，通过 ST2 受体信号传导，最初被定义为 T 辅助 2（Th2）细胞因子的诱导剂。最近，IL-33 的免疫激活潜力得到了更广泛的定义，特别是通过肥大细胞激活和中性粒细胞迁移。在这里，我们发现在佛波酯诱导的皮肤炎症模型中，与 WT 小鼠相比，ST2(-/-) 小鼠的皮肤炎症反应减少。此外，将 IL-33 注射到小鼠耳朵中会引起炎症性皮肤损伤。这种炎症反应部分依赖于肥大细胞，因为肥大细胞缺陷型小鼠（Kit(W-sh/W-sh)）对 IL-33 的反应延迟。IL-33 还将中性粒细胞募集到耳朵中，这一效应部分是通过趋化因子 KC（CXCL1）的产生增加介导的。最后，我们发现与健康皮肤相比，IL-33 在临床银屑病病变的表皮中表达上调。因此，这些结果表明 IL-33 可能在银屑病样斑块炎症中发挥作用。IL-33 靶向可能为银屑病提供新的治疗策略。
