Wu Junchao, Li Lisha, Zhang Tingrui, Lu Jiaye, Tai Zongguang, Zhu Quangang, Chen Zhongjian
School of Medicine, Shanghai University, Shanghai 200444, China; Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China.
Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China; Shanghai Engineering Research Center for Topical Chinese Medicine, Shanghai, 200443, China.
J Adv Res. 2025 Feb;68:359-374. doi: 10.1016/j.jare.2024.03.001. Epub 2024 Mar 7.
The promotion of epidermal barrier dysfunction is attributed to abnormalities in the lipid-microbiome positive feedback loop which significantly influences the imbalance of the epithelial immune microenvironment (EIME) in atopic dermatitis (AD). This imbalance encompasses impaired lamellar membrane integrity, heightened exposure to epidermal pathogens, and the regulation of innate and adaptive immunity. The lipid-microbiome loop is substantially influenced by intense adaptive immunity which is triggered by abnormal loop activity and affects the loop's integrity through the induction of atypical lipid composition and responses to dysregulated epidermal microbes. Immune responses participate in lipid abnormalities within the EIME by downregulating barrier gene expression and are further cascade-amplified by microbial dysregulation which is instigated by barrier impairment.
This review examines the relationship between abnormal lipid composition, microbiome disturbances, and immune responses in AD while progressively substantiating the crosstalk mechanism among these factors. Based on this analysis, the "lipid-microbiome" positive feedback loop, regulated by immune responses, is proposed.
The review delves into the impact of adaptive immune responses that regulate the EIME, driving AD, and investigates potential mechanisms by which lipid supplementation and probiotics may alleviate AD through the up-regulation of the epidermal barrier and modulation of immune signaling. This exploration offers support for targeting the EIME to attenuate AD.
表皮屏障功能障碍的加剧归因于脂质-微生物群正反馈回路的异常,这显著影响了特应性皮炎(AD)中上皮免疫微环境(EIME)的失衡。这种失衡包括板层膜完整性受损、表皮病原体暴露增加以及固有免疫和适应性免疫的调节。脂质-微生物群回路受到强烈适应性免疫的显著影响,这种适应性免疫由回路活动异常触发,并通过诱导非典型脂质组成和对失调表皮微生物的反应来影响回路的完整性。免疫反应通过下调屏障基因表达参与EIME内的脂质异常,并由屏障损伤引发的微生物失调进一步级联放大。
本综述探讨了AD中异常脂质组成、微生物群紊乱和免疫反应之间的关系,同时逐步证实这些因素之间的相互作用机制。基于此分析,提出了由免疫反应调节的“脂质-微生物群”正反馈回路。
本综述深入探讨了调节EIME、驱动AD的适应性免疫反应的影响,并研究了脂质补充剂和益生菌通过上调表皮屏障和调节免疫信号来缓解AD的潜在机制。这一探索为针对EIME减轻AD提供了支持。