Seminar by Dr Sophie Ugolini

Seminar Title: Neuroimmune interactions in the skin, from molecular mechanisms to therapeutic perspectives

Speaker: Dr Sophie Ugolini

Affiliations: Head of the laboratory NEURAL REGULATION OF IMMUNITY, Centre d'immunologie de Marseille-Luminy (CIML)

Sophie Ugolini is a research director (DR) at INSERM and team leader at the Marseille-Luminy Immunology Centre (CIML). Her research focuses on the biology of inflammation and immune responses to pathogens and tumours. She has studied innate immune responses from the single molecule to the systemic level, using natural killer (NK) cells as a model system. This included genetic and functional studies based on N-ethyl N-nitrosourea (ENU) mutagenesis and the use of infectious and tumour models. Her team also participated in a clinical trial using NK cells as anti-cancer agents. More recently, her laboratory has been exploring the interactions between the nervous and immune systems. In particular, the team identified new neuro-immune pathways that play a crucial role in the regulation of inflammation and tissue repair. Sophie Ugolini received several awards including the "Prix Duquesne" from the Ligue contre le cancer (2013), the "Prix Recherche" from INSERM (2012) and the Prix Dandrimont-Bénicourt from the Institut de France (2011), as well as an ERC Consolidator grant (2015).

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 repair, but the precise molecular mechanisms that regulate the balance between inflammatory and pro-repair macrophage responses during healing remain poorly understood. We demonstrated 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.