Nature (London), 2021-06, Vol.594 (7861), p.94-99
2021
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- Autor(en) / Beteiligte
- Titel
- Sensory neuron-derived TAFA4 promotes macrophage tissue repair functions
- Ist Teil von
- Nature (London), 2021-06, Vol.594 (7861), p.94-99
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. 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 Gα -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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687DOI: 10.1038/s41586-021-03563-7Titel-ID: cdi_hal_primary_oai_HAL_hal_03419356v1
- Format
- –
- Schlagworte
- Ablation, Animals, Cell Survival, Cytokines - deficiency, Cytokines - metabolism, Damage, Dendritic cells, Disease Models, Animal, Female, Fibrosis, Fibrosis - etiology, Fibrosis - metabolism, Fibrosis - pathology, Fibrosis - prevention & control, Genes, Healing, In vivo methods and tests, Inflammation, Inflammation - etiology, Inflammation - metabolism, Inflammation - pathology, Inflammation - prevention & control, Inflammatory diseases, Interleukin 10, Interleukin-10 - biosynthesis, Interleukin-10 - metabolism, Life Sciences, Macrophages, Macrophages - metabolism, Macrophages - radiation effects, Mechanoreceptors, Membrane Proteins - metabolism, Mice, Mice, Inbred C57BL, Molecular modelling, Nervous system, Neurons, Neuropeptides, Regeneration, Repair, Sensory neurons, Sensory Receptor Cells - metabolism, Sensory Receptor Cells - radiation effects, Skin, Skin - pathology, Skin - radiation effects, Sunburn, Sunburn - complications, Sunburn - etiology, Sunburn - metabolism, Sunburn - pathology, Tissue engineering, Tissues, Transcription factors, Ultraviolet radiation, Ultraviolet Rays - adverse effects, Wound Healing