Kun He, Hanxi Xiao, William A. MacDonald, Isha Mehta, Akash Kishore, Augusta Vincent, Zhongli Xu, Anuradha Ray, Wei Chen, Casey T. Weaver, Bart N. Lambrecht, Jishnu Das, Amanda C. Poholek
{"title":"IL-2与IL-10的空间微量相结合，驱动肺迁移性TH2细胞对吸入的过敏原做出反应","authors":"Kun He, Hanxi Xiao, William A. MacDonald, Isha Mehta, Akash Kishore, Augusta Vincent, Zhongli Xu, Anuradha Ray, Wei Chen, Casey T. Weaver, Bart N. Lambrecht, Jishnu Das, Amanda C. Poholek","doi":"10.1038/s41590-024-01986-8","DOIUrl":null,"url":null,"abstract":"<p>The mechanisms that guide T helper 2 (T<sub>H</sub>2) cell differentiation in barrier tissues are unclear. Here we describe the molecular pathways driving allergen-specific T<sub>H</sub>2 cells using temporal, spatial and single-cell transcriptomic tracking of house dust mite-specific T cells in mice. Differentiation and migration of lung allergen-specific T<sub>H</sub>2 cells requires early expression of the transcriptional repressor Blimp-1. Loss of Blimp-1 during priming in the lymph node ablated the formation of T<sub>H</sub>2 cells in the lung, indicating early Blimp-1 promotes T<sub>H</sub>2 cells with migratory capability. IL-2/STAT5 signals and autocrine/paracrine IL-10 from house dust mite-specific T cells were essential for Blimp-1 and subsequent GATA3 upregulation through repression of Bcl6 and Bach2. Spatial microniches of IL-2 in the lymph node supported the earliest Blimp-1<sup>+</sup>T<sub>H</sub>2 cells, demonstrating lymph node localization is a driver of T<sub>H</sub>2 initiation. Our findings identify an early requirement for IL-2-mediated spatial microniches that integrate with allergen-driven IL-10 from responding T cells to drive allergic asthma.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7000,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Spatial microniches of IL-2 combine with IL-10 to drive lung migratory TH2 cells in response to inhaled allergen\",\"authors\":\"Kun He, Hanxi Xiao, William A. MacDonald, Isha Mehta, Akash Kishore, Augusta Vincent, Zhongli Xu, Anuradha Ray, Wei Chen, Casey T. Weaver, Bart N. Lambrecht, Jishnu Das, Amanda C. Poholek\",\"doi\":\"10.1038/s41590-024-01986-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The mechanisms that guide T helper 2 (T<sub>H</sub>2) cell differentiation in barrier tissues are unclear. Here we describe the molecular pathways driving allergen-specific T<sub>H</sub>2 cells using temporal, spatial and single-cell transcriptomic tracking of house dust mite-specific T cells in mice. Differentiation and migration of lung allergen-specific T<sub>H</sub>2 cells requires early expression of the transcriptional repressor Blimp-1. Loss of Blimp-1 during priming in the lymph node ablated the formation of T<sub>H</sub>2 cells in the lung, indicating early Blimp-1 promotes T<sub>H</sub>2 cells with migratory capability. IL-2/STAT5 signals and autocrine/paracrine IL-10 from house dust mite-specific T cells were essential for Blimp-1 and subsequent GATA3 upregulation through repression of Bcl6 and Bach2. Spatial microniches of IL-2 in the lymph node supported the earliest Blimp-1<sup>+</sup>T<sub>H</sub>2 cells, demonstrating lymph node localization is a driver of T<sub>H</sub>2 initiation. Our findings identify an early requirement for IL-2-mediated spatial microniches that integrate with allergen-driven IL-10 from responding T cells to drive allergic asthma.</p>\",\"PeriodicalId\":19032,\"journal\":{\"name\":\"Nature Immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":27.7000,\"publicationDate\":\"2024-10-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41590-024-01986-8\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41590-024-01986-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
指导屏障组织中 T 辅助细胞 2（TH2）分化的机制尚不清楚。在这里，我们通过对小鼠体内的屋尘螨特异性 T 细胞进行时间、空间和单细胞转录组追踪，描述了驱动过敏原特异性 TH2 细胞的分子途径。肺过敏原特异性TH2细胞的分化和迁移需要转录抑制因子Blimp-1的早期表达。在淋巴结引物过程中失去Blimp-1会导致肺中TH2细胞的形成，这表明早期Blimp-1会促进具有迁移能力的TH2细胞。来自屋尘螨特异性T细胞的IL-2/STAT5信号和自分泌/旁分泌IL-10对Blimp-1和随后通过抑制Bcl6和Bach2上调GATA3至关重要。淋巴结中的IL-2空间微粒支持最早的Blimp-1+TH2细胞，表明淋巴结定位是TH2启动的驱动因素。我们的研究结果表明，IL-2介导的空间微区与过敏原驱动的应答T细胞产生的IL-10结合在一起，驱动过敏性哮喘的发生，这是IL-2介导的空间微区的早期需求。
Spatial microniches of IL-2 combine with IL-10 to drive lung migratory TH2 cells in response to inhaled allergen
The mechanisms that guide T helper 2 (TH2) cell differentiation in barrier tissues are unclear. Here we describe the molecular pathways driving allergen-specific TH2 cells using temporal, spatial and single-cell transcriptomic tracking of house dust mite-specific T cells in mice. Differentiation and migration of lung allergen-specific TH2 cells requires early expression of the transcriptional repressor Blimp-1. Loss of Blimp-1 during priming in the lymph node ablated the formation of TH2 cells in the lung, indicating early Blimp-1 promotes TH2 cells with migratory capability. IL-2/STAT5 signals and autocrine/paracrine IL-10 from house dust mite-specific T cells were essential for Blimp-1 and subsequent GATA3 upregulation through repression of Bcl6 and Bach2. Spatial microniches of IL-2 in the lymph node supported the earliest Blimp-1+TH2 cells, demonstrating lymph node localization is a driver of TH2 initiation. Our findings identify an early requirement for IL-2-mediated spatial microniches that integrate with allergen-driven IL-10 from responding T cells to drive allergic asthma.
期刊介绍：
Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
