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

Author

Listed:
  • Yiya Zhang

    (Central South University
    Central South University
    Central South University)

  • Tao Li

    (Central South University
    Central South University)

  • Han Zhao

    (Central South University
    Central South University)

  • Xin Xiao

    (Central South University
    Central South University)

  • Ximin Hu

    (Central South University
    Central South University)

  • Ben Wang

    (Central South University
    Central South University)

  • Yingxue Huang

    (Central South University
    Central South University)

  • Zhinan Yin

    (Jinan University
    Jinan University)

  • Yun Zhong

    (Central South University
    Central South University)

  • Yangfan Li

    (Central South University
    Central South University
    The First Affiliated Hospital of Zhengzhou University)

  • Ji Li

    (Central South University
    Central South University
    Central South University)

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.

Suggested Citation

  • Yiya Zhang & Tao Li & Han Zhao & Xin Xiao & Ximin Hu & Ben Wang & Yingxue Huang & Zhinan Yin & Yun Zhong & Yangfan Li & Ji Li, 2024. "High-sensitive sensory neurons exacerbate rosacea-like dermatitis in mice by activating γδ T cells directly," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50970-1
    DOI: 10.1038/s41467-024-50970-1
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    References listed on IDEAS

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    1. Felipe A. Pinho-Ribeiro & Liwen Deng & Dylan V. Neel & Ozge Erdogan & Himanish Basu & Daping Yang & Samantha Choi & Alec J. Walker & Simone Carneiro-Nascimento & Kathleen He & Glendon Wu & Beth Steven, 2023. "Bacteria hijack a meningeal neuroimmune axis to facilitate brain invasion," Nature, Nature, vol. 615(7952), pages 472-481, March.
    2. Lorena Riol-Blanco & Jose Ordovas-Montanes & Mario Perro & Elena Naval & Aude Thiriot & David Alvarez & Silke Paust & John N. Wood & Ulrich H. von Andrian, 2014. "Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation," Nature, Nature, vol. 510(7503), pages 157-161, June.
    3. Jessica Filtjens & Anais Roger & Linda Quatrini & Elisabeth Wieduwild & Jordi Gouilly & Guillaume Hoeffel & Rafaëlle Rossignol & Clara Daher & Guilhaume Debroas & Sandrine Henri & Claerwen M. Jones & , 2021. "Nociceptive sensory neurons promote CD8 T cell responses to HSV-1 infection," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    4. Guillaume Hoeffel & Guilhaume Debroas & Anais Roger & Rafaelle Rossignol & Jordi Gouilly & Caroline Laprie & Lionel Chasson & Pierre-Vincent Barbon & Anaïs Balsamo & Ana Reynders & Aziz Moqrich & Soph, 2021. "Sensory neuron-derived TAFA4 promotes macrophage tissue repair functions," Nature, Nature, vol. 594(7861), pages 94-99, June.
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