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 Gα_i-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.

炎症是对组织损伤的防御反应，需要严格调节以防止愈合受损。^{组织驻留巨噬细胞在组织修复1}中具有关键作用，但在愈合过程中调节炎症和促修复巨噬细胞反应之间平衡的精确分子机制仍然知之甚少。在这里，我们证明了感觉神经元在促进巨噬细胞的组织修复功能中的主要作用。在小鼠晒伤样皮肤损伤模型中，表达 Gα _{i的感觉神经元的条件消融}相互作用蛋白 (GINIP) 导致组织再生缺陷和真皮纤维化。对潜在分子机制的阐明揭示了神经肽 TAFA4 的关键作用，它是由 C 低阈值机械感受器（GINIP ⁺神经元的一个子集）在皮肤中产生的。TAFA4 在体外直接调节巨噬细胞的炎症特征。在缺乏 Tafa4的小鼠中进行的体内研究表明，TAFA4 在紫外线诱导的皮肤损伤后促进真皮巨噬细胞产生 IL-10。^{这个 TAFA4-IL-10 轴也保证了 IL-10 +} TIM4 ⁺的存活和维持真皮巨噬细胞，减少皮肤炎症，促进组织再生。这些结果揭示了由神经肽 TAFA4 驱动的神经免疫调节通路，可促进巨噬细胞的抗炎功能并防止组织损伤后的纤维化，并可能为炎症性疾病带来新的治疗前景。