科學家揭示屋塵蟎引起2型皮炎的分子機制

科學家揭示屋塵蟎引起2型皮炎的分子機制

作者：

小柯機器人

發布時間：2019/10/8 15:25:30

法國土魯斯大學Nicolas Gaudenzio和美國史丹福大學Stephen J. Galli等研究人員合作發現，屋塵蟎（HDM）會激活傷害感受器-肥大細胞簇，從而引發2型皮膚炎症。該項研究成果於2019年10月7日在線發表在《自然—免疫學》上。

研究人員發現具有半胱氨酸蛋白酶活性的HDM直接激活了肽能傷害感受器，這是產生神經肽的傷害性感覺神經元，它們表達離子通道TRPV1和Tac1（編碼神經肽物質P前體的基因）。活體成像和遺傳方法表明，HDM激活的傷害感受器通過釋放P物質以及激活肥大細胞上的陽離子分子受體MRGPRB2，來誘導與該傷害感受器相鄰的肥大細胞脫粒，從而導致過敏性皮膚炎症的進展。

這些數據表明，暴露於HDM過敏原後，TRPV1和Tac1雙陽性傷害感受器與MRGPRB2陽性肥大細胞感受簇的激活代表了過敏性皮膚反應發展中的關鍵早期事件。

據介紹，過敏性皮膚病（例如特應性皮炎）的臨床特徵是嚴重瘙癢和對廣泛分布的過敏原（包括HDM產生的過敏原）產生的2型免疫相關超敏反應。

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