痛觉感受器衍生的CGRP增强皮肤I型常规树突状细胞功能，驱动白癜风患者自身反应性CD8+ T细胞反应

IF 25.5 1区医学 Q1 IMMUNOLOGY

Immunity Pub Date : 2025-06-16 DOI:10.1016/j.immuni.2025.05.018

Xiuli Yang, Wenxiang Ding, Fangzhou Lou, Hao Xu, Anqi Sheng, Yang Sun, Xiaojie Cai, Miaoni Zhou, Fuquan Lin, Rong Jin, Xichen Zheng, Zhikai Wang, Siyu Deng, Zhenyao Xu, Taiyu Zhang, Jinke Cheng, Xingdong Zheng, Aie Xu, Honglin Wang

{"title":"痛觉感受器衍生的CGRP增强皮肤I型常规树突状细胞功能，驱动白癜风患者自身反应性CD8+ T细胞反应","authors":"Xiuli Yang, Wenxiang Ding, Fangzhou Lou, Hao Xu, Anqi Sheng, Yang Sun, Xiaojie Cai, Miaoni Zhou, Fuquan Lin, Rong Jin, Xichen Zheng, Zhikai Wang, Siyu Deng, Zhenyao Xu, Taiyu Zhang, Jinke Cheng, Xingdong Zheng, Aie Xu, Honglin Wang","doi":"10.1016/j.immuni.2025.05.018","DOIUrl":null,"url":null,"abstract":"Vitiligo is an autoimmune disease characterized by depigmented patches of skin. Autoreactive CD8+ T cells kill melanocytes in vitiligo, but the immunopathogenesis remains elusive and ideal drug targets are lacking. Through single-cell and spatial transcriptomic analysis of vitiligo lesional skin, we found that conventional type 1 dendritic cells (cDC1s) primed CD8+ T cells and highly expressed the neuropeptide calcitonin gene-related peptide (CGRP) receptor. Deletion of Nav1.8+ nociceptors, cDC1-specific ablation of the CGRP receptor, or treatment with a CGRP receptor antagonist (rimegepant) abrogated CD8+ T cell autoreactivity and prevented skin depigmentation in a mouse model of vitiligo. Conversely, CGRP administration restored vitiligo development in nociceptor-ablated mice. In a pilot study, topical application of rimegepant ointment alleviated skin depigmentation in individuals with vitiligo. Taken together, our results reveal that nociceptor-derived CGRP promotes cDC1-CD8+ T cell interactions and highlight CGRP receptor antagonism as a potential therapeutic strategy for treating vitiligo.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"44 1","pages":""},"PeriodicalIF":25.5000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Nociceptor-derived CGRP enhances dermal type I conventional dendritic cell function to drive autoreactive CD8+ T cell responses in vitiligo\",\"authors\":\"Xiuli Yang, Wenxiang Ding, Fangzhou Lou, Hao Xu, Anqi Sheng, Yang Sun, Xiaojie Cai, Miaoni Zhou, Fuquan Lin, Rong Jin, Xichen Zheng, Zhikai Wang, Siyu Deng, Zhenyao Xu, Taiyu Zhang, Jinke Cheng, Xingdong Zheng, Aie Xu, Honglin Wang\",\"doi\":\"10.1016/j.immuni.2025.05.018\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Vitiligo is an autoimmune disease characterized by depigmented patches of skin. Autoreactive CD8+ T cells kill melanocytes in vitiligo, but the immunopathogenesis remains elusive and ideal drug targets are lacking. Through single-cell and spatial transcriptomic analysis of vitiligo lesional skin, we found that conventional type 1 dendritic cells (cDC1s) primed CD8+ T cells and highly expressed the neuropeptide calcitonin gene-related peptide (CGRP) receptor. Deletion of Nav1.8+ nociceptors, cDC1-specific ablation of the CGRP receptor, or treatment with a CGRP receptor antagonist (rimegepant) abrogated CD8+ T cell autoreactivity and prevented skin depigmentation in a mouse model of vitiligo. Conversely, CGRP administration restored vitiligo development in nociceptor-ablated mice. In a pilot study, topical application of rimegepant ointment alleviated skin depigmentation in individuals with vitiligo. Taken together, our results reveal that nociceptor-derived CGRP promotes cDC1-CD8+ T cell interactions and highlight CGRP receptor antagonism as a potential therapeutic strategy for treating vitiligo.\",\"PeriodicalId\":13269,\"journal\":{\"name\":\"Immunity\",\"volume\":\"44 1\",\"pages\":\"\"},\"PeriodicalIF\":25.5000,\"publicationDate\":\"2025-06-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.immuni.2025.05.018\",\"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":"Immunity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.immuni.2025.05.018","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

白癜风是一种自身免疫性疾病，其特征是皮肤色素沉着。自身反应性CD8+ T细胞在白癜风中杀死黑色素细胞，但其免疫机制尚不明确，且缺乏理想的药物靶点。通过对白癜风病变皮肤的单细胞和空间转录组学分析，我们发现常规1型树突状细胞（cDC1s）引发CD8+ T细胞，并高表达神经肽降钙素基因相关肽（CGRP）受体。在白癜风小鼠模型中，缺失Nav1.8+伤害感受器，cdc1特异性消融CGRP受体，或使用CGRP受体拮抗剂（rimegepant）治疗可消除CD8+ T细胞的自身反应性，并防止皮肤色素脱色。相反，CGRP给药恢复了伤害感受器消融小鼠白癜风的发展。在一项初步研究中，局部应用利美康软膏减轻了白癜风患者的皮肤色素沉着。综上所述，我们的研究结果揭示了伤害感受器衍生的CGRP促进cDC1-CD8+ T细胞的相互作用，并强调了CGRP受体拮抗剂作为治疗白癜风的潜在治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Nociceptor-derived CGRP enhances dermal type I conventional dendritic cell function to drive autoreactive CD8+ T cell responses in vitiligo

查看原文本刊更多论文

Nociceptor-derived CGRP enhances dermal type I conventional dendritic cell function to drive autoreactive CD8+ T cell responses in vitiligo

Vitiligo is an autoimmune disease characterized by depigmented patches of skin. Autoreactive CD8⁺ T cells kill melanocytes in vitiligo, but the immunopathogenesis remains elusive and ideal drug targets are lacking. Through single-cell and spatial transcriptomic analysis of vitiligo lesional skin, we found that conventional type 1 dendritic cells (cDC1s) primed CD8⁺ T cells and highly expressed the neuropeptide calcitonin gene-related peptide (CGRP) receptor. Deletion of Na_v1.8⁺ nociceptors, cDC1-specific ablation of the CGRP receptor, or treatment with a CGRP receptor antagonist (rimegepant) abrogated CD8⁺ T cell autoreactivity and prevented skin depigmentation in a mouse model of vitiligo. Conversely, CGRP administration restored vitiligo development in nociceptor-ablated mice. In a pilot study, topical application of rimegepant ointment alleviated skin depigmentation in individuals with vitiligo. Taken together, our results reveal that nociceptor-derived CGRP promotes cDC1-CD8⁺ T cell interactions and highlight CGRP receptor antagonism as a potential therapeutic strategy for treating vitiligo.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Immunity 医学-免疫学

CiteScore

49.40

自引率

2.20%

发文量

205

审稿时长

6 months

期刊介绍： Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.