Sensory neuron-derived TAFA4 promotes macrophage tissue repair functions

Autor: Anais Roger, Ana Reynders, Aziz Moqrich, Jordi Gouilly, Rafaelle Rossignol, Guillaume Hoeffel, Sophie Ugolini, Guilhaume Debroas, Pierre-Vincent Barbon, Lionel Chasson, Anaïs Balsamo, Caroline Laprie
Přispěvatelé: Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Institute of Developmental Biology and Cancer (IBDC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), ANR-14-CE14-0009,SensorImmune,Régulation de la réponse immunitaire par le système nerveux(2014), European Project: 648768,H2020,ERC-2014-CoG,NEURIMMUNE(2015), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Poulain, Sébastien, Appel à projets générique - Régulation de la réponse immunitaire par le système nerveux - - SensorImmune2014 - ANR-14-CE14-0009 - Appel à projets générique - VALID, Neural regulation of immunity - NEURIMMUNE - - H20202015-10-01 - 2020-09-30 - 648768 - VALID
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Nature
Nature, Nature Publishing Group, 2021, 594 (7861), pp.94-99. ⟨10.1038/s41586-021-03563-7⟩
Nature, 2021, 594 (7861), pp.94-99. ⟨10.1038/s41586-021-03563-7⟩
ISSN: 0028-0836
1476-4679
1476-4687
DOI: 10.1038/s41586-021-03563-7⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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