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    Sensory neurons regulate dermal macrophage dynamic and functions in tissue repair

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    Séminaire de l'Institut Cochin

    Lundi 18 novembre 2019 - 12h00 - Salle de conférence Rosalind Franklin, 2ème étage

     


    Guillaume Hoeffel

    Aix Marseille Univ, CNRS, INSERM, CIML,
    Centre d'Immunologie de Marseille-Luminy, Marseille, France

     

     invité par Florence Niedergang

    Institut Cochin, 22 rue Méchain, 75014 Paris

     

    Résumé

    The existence of a bidirectional communication between the nervous and the immune system is now well accepted. Tissue-resident macrophages are key players in tissue homeostasis and highly rely on their niche microenvironment to acquire and sustain their functions throughout the lifespan. In the skin, the dense sensory neuron network could provide such signaling to dermal macrophages.

    We identified here a particular subset of sensory neurons called low-threshold mechanoreceptor type C (C-LTMR) as crucial in tissue repair after sunburn-like lesion. Depletion of these neurons increased tissue-damage and residual dermal fibrotic scar upon UV irradiation. Exploring the ontogeny of dermal macrophages, we identified that embryonic-derived long-lived macrophages are rapidly outnumbered by monocytes-derived macrophages in UV-irradiated mice. Depletion of sensory neurons increased inflammatory monocyte infiltration concomitantly with a defect in specific anti-inflammatory dermal macrophage subsets. Finally, we identified a particular neuropeptide promoting the anti-inflammatory properties of dermal macrophages. Without this neuropeptide, dermal macrophages become defective in resolving the skin inflammation after UV exposure, leading to fibrotic scar.

    Our results suggest that sensory neurons could provide signals allowing dermal-resident macrophages to optimize their pro-repair activities during inflammation and protect the skin from overwhelming fibrosis. 

     

    Quelques publications

    • Hoeffel G & Ginhoux F. Fetal monocytes and the origins of Tissue-resident Macrophages. 2018 Cell Immunol. Aug; 330:5-15.
    • Hoeffel G, Chen J, Lavin Y, Low D, Almeida F, See P, Beaudin AE, Lum J, Low I, Forsberg C, Podinger M, Zolezzi F, Larib A, Ng LG, Chan JKY, Greter M, Becher B, Samokhvalov IM, Merad M, and Ginhoux F. C-Myb+ erythro-myeloid progenitors-derived fetal monocytes give rise to tissue-resident macrophages. Immunity. 2015 Apr 21;42(4):665-78.
    • Hoeffel G, Wang Y, Greter M, See P, Teo P, Malleret B, Leboeuf M, Low D, Oller G, Almeida F, Choy SH, Grisotto M, Renia L, Conway SJ, Stanley ER, Chan JK, Ng LG, Samokhvalov IM, Merad M, Ginhoux F. Adult Langerhans cells derive predominantly from fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J Exp Med 2012 Jun 4; 209 (6):1167-81. 

     

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