棕酸通过通过驱动TRPV1和MRGPRB2S-palmitoylation调节SGK1/NEDD4L相关的皮肤神经免疫炎症来加剧亚托皮性皮肤炎
Bangtao Chen1, Jing Yang1,2, Tingting Song2
1Department of Dermatology, School of Medicine, Chongqing University Three Gorges Hospital, Chongqing University, Chongqing, 404100, People's Republic of China.
概括
在阿托皮性皮肤炎 (AD) 中皮肤上增加的棕酸 (PA) 促进了TRPV1 S-棕化在恶性受体和MRGPRB2 S-棕化在巨细胞中,加剧了AD. 这一途径涉及SGK1/NEDD4L监管.
科学领域:
- 皮肤病学 皮肤病学
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
背景情况:
- 亚托皮炎 (AD) 涉及皮肤屏障功能障碍,免疫细胞和感觉神经元之间的复杂相互作用.
- 棕酸 (PA) 是一种常见的脂肪酸,已与皮肤炎症有关,但其在AD病变发生过程中的确切作用尚不清楚.
- 转移性受体潜在的瓦尼洛伊德-1 (TRPV1) 在恶性受体上和Mas相关的G蛋白结合受体B2 (MRGPRB2) 在巨细胞上是神经免疫通信的关键参与者.
研究的目的:
- 为了阐明皮肤棕酸 (PA) 在调节TRPV1在恶性受体和MRGPRB2在瘤细胞 (MCs) 中的作用,在阿托皮性皮肤炎 (AD) 的背景下.
- 研究PA介导信号与AD中的SGK1/NEDD4L通路之间的关联.
- 了解PA对AD中神经免疫轴激活的下游影响.
主要方法:
- 使用了条件淘汰 (cKO) 鼠标模型,在恶感受体和MC中具有特定基因缺失 (nedd4l, sgk1, mrgprb2).
- 用皮内PA,物质P (SP) 和棕化抑制剂 (2BP) 诱导和调节特定的信号通路.
- 在体外机理学研究中采用隔离的背部根 (DRGs) 和骨髓衍生性巨细胞 (mBMMCs).
主要成果:
- 皮肤PA水平在AD小鼠中升高,与DRG中TRPV1 S-palmitoylation和SP产量的增加相关,以及MC中MRGPRB2 S-palmitoylation和试酶释放.
- 在 nociceptors 中的 NEDD4L 敲除增强了 SP 表达,而 SGK1 敲除则显示出相反的效果; PA 进一步调节了这些反应.
- 在MC中,PA增强了SP诱导的MRGPRB2 S-palmitoylation和酶释放,NEDD4L和SGK1影响了这些过程.
- TRPV1的S-palmitoylation是由PA和角质细胞衍生因素促进的,而在特定的NEDD4L/SGK1酸化状态下,MRGPRB2的减少被抑制.
结论:
- 增加的皮肤PA加剧AD通过驱动TRPV1 S-palmitoylation在恶性受体和MRGPRB2 S-palmitoylation在MCs,创造一个亲炎轴.
- 该SGK1/NEDD4L通路在调节TRPV1和MRGPRB2S-palmitoylation以及AD中随后的细胞反应方面发挥着关键作用.
- 由NEDD4L和SGK1调节的S-palmitoylation是将PA与在亚托皮炎中增强的神经免疫活性联系起来的关键机制.
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