The immune system has a critical role in orchestrating tissue healing. As a result, regenerative strategies that control immune components have proved effective^1,2. This is particularly relevant when immune dysregulation that results from conditions such as diabetes or advanced age impairs tissue healing following injury^2,3. Nociceptive sensory neurons have a crucial role as immunoregulators and exert both protective and harmful effects depending on the context^{4,5,6,7,8,9,10,11,12}. However, how neuro–immune interactions affect tissue repair and regeneration following acute injury is unclear. Here we show that ablation of the Na_V1.8 nociceptor impairs skin wound repair and muscle regeneration after acute tissue injury. Nociceptor endings grow into injured skin and muscle tissues and signal to immune cells through the neuropeptide calcitonin gene-related peptide (CGRP) during the healing process. CGRP acts via receptor activity-modifying protein 1 (RAMP1) on neutrophils, monocytes and macrophages to inhibit recruitment, accelerate death, enhance efferocytosis and polarize macrophages towards a pro-repair phenotype. The effects of CGRP on neutrophils and macrophages are mediated via thrombospondin-1 release and its subsequent autocrine and/or paracrine effects. In mice without nociceptors and diabetic mice with peripheral neuropathies, delivery of an engineered version of CGRP accelerated wound healing and promoted muscle regeneration. Harnessing neuro–immune interactions has potential to treat non-healing tissues in which dysregulated neuro–immune interactions impair tissue healing.

免疫系统在协调组织愈合方面发挥着关键作用。因此，控制免疫成分的再生策略已被证明是有效的^1,2。当糖尿病或高龄等疾病导致的免疫失调损害损伤后的组织愈合时，这一点尤其重要^2,3。伤害性感觉神经元作为免疫调节器发挥着至关重要的作用，并根据具体情况发挥保护和有害作用^{4,5,6,7,8,9,10,11,12}。然而，神经免疫相互作用如何影响急性损伤后的组织修复和再生尚不清楚。在这里，我们表明 Na _V 1.8 伤害感受器的消融会损害急性组织损伤后的皮肤伤口修复和肌肉再生。伤害感受器末梢生长到受伤的皮肤和肌肉组织中，并在愈合过程中通过神经肽降钙素基因相关肽（CGRP）向免疫细胞发出信号。 CGRP 通过受体活性修饰蛋白 1 (RAMP1) 作用于中性粒细胞、单核细胞和巨噬细胞，抑制招募、加速死亡、增强胞吞作用并使巨噬细胞极化至促修复表型。 CGRP 对中性粒细胞和巨噬细胞的作用是通过血小板反应蛋白-1 的释放及其随后的自分泌和/或旁分泌作用介导的。在没有伤害感受器的小鼠和患有周围神经病变的糖尿病小鼠中，传递工程化版本的 CGRP 可加速伤口愈合并促进肌肉再生。利用神经-免疫相互作用有可能治疗不可愈合的组织，在这些组织中，神经-免疫相互作用失调会损害组织愈合。