High-sensitive sensory neurons exacerbate rosacea-like dermatitis in mice by activating γδ T cells directly

Yiya Zhang, Tao Li, Han Zhao, Xin Xiao, Ximin Hu, Ben Wang, Yingxue Huang, Zhinan Yin, Yun Zhong, Yangfan Li () and Ji Li ()
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Yiya Zhang: Central South University
Tao Li: Central South University
Han Zhao: Central South University
Xin Xiao: Central South University
Ximin Hu: Central South University
Ben Wang: Central South University
Yingxue Huang: Central South University
Zhinan Yin: Jinan University
Yun Zhong: Central South University
Yangfan Li: Central South University
Ji Li: Central South University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Rosacea patients show facial hypersensitivity to stimulus factors (such as heat and capsaicin); however, the underlying mechanism of this hyperresponsiveness remains poorly defined. Here, we show capsaicin stimulation in mice induces exacerbated rosacea-like dermatitis but has no apparent effect on normal skin. Nociceptor ablation substantially reduces the hyperresponsiveness of rosacea-like dermatitis. Subsequently, we find that γδ T cells express Ramp1, the receptor of the neuropeptide CGRP, and are in close contact with these nociceptors in the skin. γδ T cells are significantly increased in rosacea skin lesions and can be further recruited and activated by neuron-secreted CGRP. Rosacea-like dermatitis is reduced in T cell receptor δ-deficient (Tcrd−/−) mice, and the nociceptor-mediated aggravation of rosacea-like dermatitis is also reduced in these mice. In vitro experiments show that CGRP induces IL17A secretion from γδ T cells by regulating inflammation-related and metabolism-related pathways. Finally, rimegepant, a CGRP receptor antagonist, shows efficacy in the treatment of rosacea-like dermatitis. In conclusion, our findings demonstrate a neuron-CGRP-γδT cell axis that contributes to the hyperresponsiveness of rosacea, thereby showing that targeting CGRP is a potentially effective therapeutic strategy for rosacea.

Date: 2024
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DOI: 10.1038/s41467-024-50970-1

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