IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v594y2021i7861d10.1038_s41586-021-03563-7.html
   My bibliography  Save this article

Sensory neuron-derived TAFA4 promotes macrophage tissue repair functions

Author

Listed:
  • Guillaume Hoeffel

    (Aix Marseille Univ., CNRS, INSERM, CIML, Centre d’Immunologie de Marseille-Luminy)

  • Guilhaume Debroas

    (Aix Marseille Univ., CNRS, INSERM, CIML, Centre d’Immunologie de Marseille-Luminy)

  • Anais Roger

    (Aix Marseille Univ., CNRS, INSERM, CIML, Centre d’Immunologie de Marseille-Luminy)

  • Rafaelle Rossignol

    (Aix Marseille Univ., CNRS, INSERM, CIML, Centre d’Immunologie de Marseille-Luminy)

  • Jordi Gouilly

    (Aix Marseille Univ., CNRS, INSERM, CIML, Centre d’Immunologie de Marseille-Luminy)

  • Caroline Laprie

    (Aix Marseille Univ., CNRS, INSERM, CIML, Centre d’Immunologie de Marseille-Luminy)

  • Lionel Chasson

    (Aix Marseille Univ., CNRS, INSERM, CIML, Centre d’Immunologie de Marseille-Luminy)

  • Pierre-Vincent Barbon

    (Aix Marseille Univ., CNRS, INSERM, CIML, Centre d’Immunologie de Marseille-Luminy)

  • Anaïs Balsamo

    (Aix Marseille Univ., CNRS, INSERM, CIML, Centre d’Immunologie de Marseille-Luminy)

  • Ana Reynders

    (Aix Marseille Univ., CNRS, IBDM, Institut de Biologie du Développement de Marseille)

  • Aziz Moqrich

    (Aix Marseille Univ., CNRS, IBDM, Institut de Biologie du Développement de Marseille)

  • Sophie Ugolini

    (Aix Marseille Univ., CNRS, INSERM, CIML, Centre d’Immunologie de Marseille-Luminy)

Abstract

Inflammation is a defence response to tissue damage that requires tight regulation in order to prevent impaired healing. Tissue-resident macrophages have a key role in tissue repair1, but the precise molecular mechanisms that regulate the balance between inflammatory and pro-repair macrophage responses during healing remain poorly understood. Here we demonstrate a major role for sensory neurons in promoting the tissue-repair function of macrophages. In a sunburn-like model of skin damage in mice, the conditional ablation of sensory neurons expressing the Gαi-interacting protein (GINIP) results in defective tissue regeneration and in dermal fibrosis. Elucidation of the underlying molecular mechanisms revealed a crucial role for the neuropeptide TAFA4, which is produced in the skin by C-low threshold mechanoreceptors—a subset of GINIP+ neurons. TAFA4 modulates the inflammatory profile of macrophages directly in vitro. In vivo studies in Tafa4-deficient mice revealed that TAFA4 promotes the production of IL-10 by dermal macrophages after UV-induced skin damage. This TAFA4–IL-10 axis also ensures the survival and maintenance of IL-10+TIM4+ dermal macrophages, reducing skin inflammation and promoting tissue regeneration. These results reveal a neuroimmune regulatory pathway driven by the neuropeptide TAFA4 that promotes the anti-inflammatory functions of macrophages and prevents fibrosis after tissue damage, and could lead to new therapeutic perspectives for inflammatory diseases.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:nature:v:594:y:2021:i:7861:d:10.1038_s41586-021-03563-7
    DOI: 10.1038/s41586-021-03563-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-021-03563-7
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-021-03563-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. T. Hautz & S. Salcher & M. Fodor & G. Sturm & S. Ebner & A. Mair & M. Trebo & G. Untergasser & S. Sopper & B. Cardini & A. Martowicz & J. Hofmann & S. Daum & M. Kalb & T. Resch & F. Krendl & A. Weisse, 2023. "Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Benoit Stijlemans & Patrick Baetselier & Inge Molle & Laurence Lecordier & Erika Hendrickx & Ema Romão & Cécile Vincke & Wendy Baetens & Steve Schoonooghe & Gholamreza Hassanzadeh-Ghassabeh & Hannelie, 2024. "Q586B2 is a crucial virulence factor during the early stages of Trypanosoma brucei infection that is conserved amongst trypanosomatids," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. 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.
    4. Min Jung & Michelle Dourado & James Maksymetz & Amanda Jacobson & Benjamin I. Laufer & Miriam Baca & Oded Foreman & David H. Hackos & Lorena Riol-Blanco & Joshua S. Kaminker, 2023. "Cross-species transcriptomic atlas of dorsal root ganglia reveals species-specific programs for sensory function," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:594:y:2021:i:7861:d:10.1038_s41586-021-03563-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.