PDF(Pubmed)
Abstract：
Atopic dermatitis (AD) is a persistent skin disease typified by symptoms of dry skin and recurrent eczema. Patients with AD are at heightened risk for Staphylococcus aureus infection. Group 2 innate lymphoid cells (ILC2s) are mainly activated by epithelial cell-derived cytokines IL-33 and involved in the pathogenesis of AD. However, little is known about the effect of skin delipidization on the epithelial cell-derived cytokines and dermal ILC2s in AD. In our study, we investigated the mechanism by which S. aureus infection modulates and exacerbates the pathogenesis of dry skin, leading to type 2 inflammation in the context of innate immunity. In vivo, we found that S. aureus infection aggravated delipidization-induced dermal IL-33 release and dermal ILC2 accumulation, which exacerbated skin inflammation. We also noticed that Il33fl/fl K14cre mice and Tlr2-/- mice exhibited attenuated skin inflammation. In vitro, treatment with necroptosis inhibitors reduced IL-33 release from S. aureus-infected keratinocytes. Mechanistically, we observed an increase in the necroptosis-associated kinases, MLKL and RIPK3, in S. aureus-infected mice, indicating that IL-33 release was associated with necroptotic cell death responses. Our results reveal that S. aureus infection-elicited keratinocyte necroptosis contributes to IL-33-mediated type 2 inflammation, which exacerbates the pathogenesis of dry skin.
摘要：
特应性皮炎(AD)是以皮肤干燥和复发性湿疹为代表的持续性皮肤病。AD患者患金黄色葡萄球菌的风险增加(S.金黄色葡萄球菌）感染。第2组固有淋巴细胞(ILC2s)主要由上皮细胞来源的细胞因子IL-33激活,参与AD的发病。然而,关于皮肤脱脂对AD中上皮细胞衍生的细胞因子和真皮ILC2s的影响知之甚少。在我们的研究中,我们研究了金黄色葡萄球菌感染调节和加剧皮肤干燥的发病机制，在先天免疫的背景下导致2型炎症。在体内,我们发现金黄色葡萄球菌感染加重了脱脂诱导的皮肤IL-33释放和皮肤ILC2积累，加剧了皮肤炎症.我们还注意到Il33f/fK14cre小鼠和Tlr2-/-小鼠表现出减弱的皮肤炎症。体外，用坏死凋亡抑制剂治疗减少了金黄色葡萄球菌感染的角质形成细胞的IL-33释放。机械上,我们观察到坏死相关激酶的增加，MLKL和RIPK3，在金黄色葡萄球菌感染的小鼠中，表明IL-33释放与坏死细胞死亡反应相关。我们的结果表明，金黄色葡萄球菌感染引起的角质形成细胞坏死有助于IL-33介导的2型炎症，这加剧了皮肤干燥的发病机理。
