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Immunity

Immunity

IF: 26.3
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Nociceptor-derived CGRP enhances dermal type I conventional dendritic cell function to drive autoreactive CD8+ T cell responses in vitiligo

Published:16 June 2025 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

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.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Rimegepant 1289023-67-1 C28H28F2N6O3 224 suppliers $43.00-$15225.00
Rimegepant 1289023-67-1 C28H28F2N6O3 224 suppliers $43.00-$15225.00
Rimegepant 1289023-67-1 C28H28F2N6O3 224 suppliers $43.00-$15225.00
Rimegepant 1289023-67-1 C28H28F2N6O3 224 suppliers $43.00-$15225.00

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