Sensory neuron-derived TAFA4 promotes macrophage tissue repair functions

Guillaume Hoeffel (), Guilhaume Debroas, Anais Roger, Rafaelle Rossignol, Jordi Gouilly, Caroline Laprie, Lionel Chasson, Pierre-Vincent Barbon, Anaïs Balsamo, Ana Reynders, Aziz Moqrich and Sophie Ugolini ()
Additional contact information
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

Nature, 2021, vol. 594, issue 7861, 94-99

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41586-021-03563-7 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:594:y:2021:i:7861:d:10.1038_s41586-021-03563-7

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-03563-7

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().