澳大利亚莫纳什大学Mikaël M. Martino课题组发现，CGRP感觉神经元通过中性粒细胞和巨噬细胞促进组织愈合。2024年3月27日，《自然》杂志在线发表了这项成果。

研究人员发现敲减Na_V1.8神经感受器会损害急性组织损伤后的皮肤伤口修复和肌肉再生。痛觉感受器末梢长入受伤的皮肤和肌肉组织，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通过中性粒细胞、单核细胞和巨噬细胞上的受体活性修饰蛋白1（RAMP1）发挥作用，抑制中性粒细胞、单核细胞和巨噬细胞的募集，加速死亡，增强胞葬作用，并将巨噬细胞极化为促进修复的表型。

CGRP对中性粒细胞和巨噬细胞的影响是通过血小板应答蛋白-1的释放，及其随后的自分泌和/或旁分泌效应介导的。在没有痛觉感受器的小鼠和患有周围神经病的糖尿病小鼠中，输送一种工程版CGRP可加速伤口愈合并促进肌肉再生。神经-免疫相互作用失调会损害组织愈合，利用神经-免疫相互作用有可能治疗这种组织愈合不良的情况。

据悉，免疫系统在协调组织愈合方面起着至关重要的作用。因此，控制免疫成分的再生策略已被证明是有效的。当糖尿病或高龄等疾病导致的免疫失调影响损伤后的组织愈合时，这一点尤为重要。痛觉神经元作为免疫调节因子发挥着至关重要的作用，并根据不同的环境发挥着保护和有害作用。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。

附：英文原文

Title: CGRP sensory neurons promote tissue healing via neutrophils and macrophages

Author: Lu, Yen-Zhen, Nayer, Bhavana, Singh, Shailendra Kumar, Alshoubaki, Yasmin K., Yuan, Elle, Park, Anthony J., Maruyama, Kenta, Akira, Shizuo, Martino, Mikal M.

Issue&Volume: 2024-03-27

Abstract: The immune system has a critical role in orchestrating tissue healing. As a result, regenerative strategies that control immune components have proved effective1,2. This is particularly relevant when immune dysregulation that results from conditions such as diabetes or advanced age impairs tissue healing following injury2,3. Nociceptive sensory neurons have a crucial role as immunoregulators and exert both protective and harmful effects depending on the context4,5,6,7,8,9,10,11,12. However, how neuro–immune interactions affect tissue repair and regeneration following acute injury is unclear. Here we show that ablation of the NaV1.8 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.

DOI: 10.1038/s41586-024-07237-y

Source: https://www.nature.com/articles/s41586-024-07237-y