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

• DOI: 10.1038/s41467-024-50970-1
• Publication Date: 2024-08-23T23:46:02Z
• Authors: Yiya Zhang; Tao Li; Han Zhao; Xin Xiao; Ximin Hu; Ben Wang; Yingxue Huang; Zhinan Yin; Yun Zhong; Yangfan Li; Ji Li
• Keywords: Nociceptor; Capsaicin; Resiniferatoxin

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 capsaicin stimulation in mice induces exacerbated rosacea-like dermatitis but has no apparent effect on normal skin. Nociceptor ablation substantially reduces dermatitis. Subsequently, find that γδ T cells express Ramp1, receptor neuropeptide CGRP, are close contact with these nociceptors significantly increased rosacea skin lesions can be further recruited activated by neuron-secreted CGRP. Rosacea-like is reduced cell δ-deficient (Tcrd−/−) mice, nociceptor-mediated aggravation also mice. In vitro experiments CGRP IL17A secretion from regulating inflammation-related metabolism-related pathways. Finally, rimegepant, a antagonist, shows efficacy treatment conclusion, our findings demonstrate neuron-CGRP-γδT axis contributes rosacea, thereby showing targeting potentially effective therapeutic strategy for rosacea. common chronic inflammatory cutaneous disease pepper stimulation. Here authors use mouse model functions nociceptors, response involvement like-disease.