Peter W. West, Jérémy Chéret, Rajia Bahri, Orsolya Kiss, Zining Wu, Colin H. Macphee, Silvia Bulfone-Paus
{"title":"MRGPRX2-Substance P 通路调控肥大细胞迁移","authors":"Peter W. West, Jérémy Chéret, Rajia Bahri, Orsolya Kiss, Zining Wu, Colin H. Macphee, Silvia Bulfone-Paus","doi":"10.1016/j.isci.2024.110984","DOIUrl":null,"url":null,"abstract":"<p>Mast cells (MC) are tissue-resident immune cells known to degranulate in response to FcεRI crosslinking or MRGPRX2 engagement. MCs are found close to nerves, but the mechanisms that regulate this privileged localization remain unclear. Here, we investigated MRGPRX2 expression patterns and specific activities in MCs. We show that MRGPRX2 expression is heterogeneous in human MC progenitors and mature MCs. Substance P (SP) is a rapid and specific activator of MRGPRX2, and long-term supplementation of MCs with SP expands MRGPRX2-expressing cells.</p><p>While high concentrations of SP induce rapid MC degranulation, low concentrations prompt immature MC chemotaxis. Lastly, we demonstrate that in inflammatory skin conditions like psoriasis, the number of MRGPRX2<sup>+</sup> MCs is increased, and during <em>in vitro</em> skin re-innervation, MRGPRX2<sup>+</sup> MCs preferentially reside in proximity to and migrate towards SP<sup>+</sup> nerve fibres. This indicates that SP-MRGPRX2 signalling defines MC positioning and relocation within tissues and promotes immune cell-nerve fibre communication.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The MRGPRX2-Substance P pathway regulates mast cell migration\",\"authors\":\"Peter W. West, Jérémy Chéret, Rajia Bahri, Orsolya Kiss, Zining Wu, Colin H. Macphee, Silvia Bulfone-Paus\",\"doi\":\"10.1016/j.isci.2024.110984\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Mast cells (MC) are tissue-resident immune cells known to degranulate in response to FcεRI crosslinking or MRGPRX2 engagement. MCs are found close to nerves, but the mechanisms that regulate this privileged localization remain unclear. Here, we investigated MRGPRX2 expression patterns and specific activities in MCs. We show that MRGPRX2 expression is heterogeneous in human MC progenitors and mature MCs. Substance P (SP) is a rapid and specific activator of MRGPRX2, and long-term supplementation of MCs with SP expands MRGPRX2-expressing cells.</p><p>While high concentrations of SP induce rapid MC degranulation, low concentrations prompt immature MC chemotaxis. Lastly, we demonstrate that in inflammatory skin conditions like psoriasis, the number of MRGPRX2<sup>+</sup> MCs is increased, and during <em>in vitro</em> skin re-innervation, MRGPRX2<sup>+</sup> MCs preferentially reside in proximity to and migrate towards SP<sup>+</sup> nerve fibres. This indicates that SP-MRGPRX2 signalling defines MC positioning and relocation within tissues and promotes immune cell-nerve fibre communication.</p>\",\"PeriodicalId\":342,\"journal\":{\"name\":\"iScience\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"iScience\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1016/j.isci.2024.110984\",\"RegionNum\":2,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"iScience","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1016/j.isci.2024.110984","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
The MRGPRX2-Substance P pathway regulates mast cell migration
Mast cells (MC) are tissue-resident immune cells known to degranulate in response to FcεRI crosslinking or MRGPRX2 engagement. MCs are found close to nerves, but the mechanisms that regulate this privileged localization remain unclear. Here, we investigated MRGPRX2 expression patterns and specific activities in MCs. We show that MRGPRX2 expression is heterogeneous in human MC progenitors and mature MCs. Substance P (SP) is a rapid and specific activator of MRGPRX2, and long-term supplementation of MCs with SP expands MRGPRX2-expressing cells.
While high concentrations of SP induce rapid MC degranulation, low concentrations prompt immature MC chemotaxis. Lastly, we demonstrate that in inflammatory skin conditions like psoriasis, the number of MRGPRX2+ MCs is increased, and during in vitro skin re-innervation, MRGPRX2+ MCs preferentially reside in proximity to and migrate towards SP+ nerve fibres. This indicates that SP-MRGPRX2 signalling defines MC positioning and relocation within tissues and promotes immune cell-nerve fibre communication.
期刊介绍:
Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results.
We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.