法国图卢兹大学Nicolas Gaudenzio和美国斯坦福大学Stephen J. Galli等研究人员合作发现，屋尘螨（HDM）会激活伤害感受器-肥大细胞簇，从而引发2型皮肤炎症。该项研究成果于2019年10月7日在线发表在《自然—免疫学》上。

研究人员发现具有半胱氨酸蛋白酶活性的HDM直接激活了肽能伤害感受器，这是产生神经肽的伤害性感觉神经元，它们表达离子通道TRPV1和Tac1（编码神经肽物质P前体的基因）。活体成像和遗传方法表明，HDM激活的伤害感受器通过释放P物质以及激活肥大细胞上的阳离子分子受体MRGPRB2，来诱导与该伤害感受器相邻的肥大细胞脱粒，从而导致过敏性皮肤炎症的进展。

这些数据表明，暴露于HDM过敏原后，TRPV1和Tac1双阳性伤害感受器与MRGPRB2阳性肥大细胞感受簇的激活代表了过敏性皮肤反应发展中的关键早期事件。

据介绍，过敏性皮肤病（例如特应性皮炎）的临床特征是严重瘙痒和对广泛分布的过敏原（包括HDM产生的过敏原）产生的2型免疫相关超敏反应。

附：英文原文

Title: House dust mites activate nociceptor–mast cell clusters to drive type 2 skin inflammation

Author: Nadine Serhan, Lilian Basso, Riccardo Sibilano, Camille Petitfils, James Meixiong, Chrystelle Bonnart, Laurent L. Reber, Thomas Marichal, Philipp Starkl, Nicolas Cenac, Xinzhong Dong, Mindy Tsai, Stephen J. Galli, Nicolas Gaudenzio

Issue&Volume: 2019-10-07

Abstract: 

Allergic skin diseases, such as atopic dermatitis, are clinically characterized by severe itching and type 2 immunity-associated hypersensitivity to widely distributed allergens, including those derived from house dust mites (HDMs). Here we found that HDMs with cysteine protease activity directly activated peptidergic nociceptors, which are neuropeptide-producing nociceptive sensory neurons that express the ion channel TRPV1 and Tac1, the gene encoding the precursor for the neuropeptide substance P. Intravital imaging and genetic approaches indicated that HDM-activated nociceptors drive the development of allergic skin inflammation by inducing the degranulation of mast cells contiguous to such nociceptors, through the release of substance P and the activation of the cationic molecule receptor MRGPRB2 on mast cells. These data indicate that, after exposure to HDM allergens, activation of TRPV1+Tac1+ nociceptor–MRGPRB2+ mast cell sensory clusters represents a key early event in the development of allergic skin reactions.

DOI: 10.1038/s41590-019-0493-z

Source: https://www.nature.com/articles/s41590-019-0493-z