| First Author | Yang X | Year | 2025 |
| Journal | Immunity | Volume | 58 |
| Issue | 8 | Pages | 2086-2103.e9 |
| PubMed ID | 40527324 | Mgi Jnum | J:371958 |
| Mgi Id | MGI:8236149 | Doi | 10.1016/j.immuni.2025.05.018 |
| Citation | Yang X, et al. (2025) Nociceptor-derived CGRP enhances dermal type I conventional dendritic cell function to drive autoreactive CD8(+) T cell responses in vitiligo. Immunity 58(8):2086-2103.e9 |
| abstractText | 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(v)1.8(+) 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. |
