小柯机器人

法国艾克斯-马赛大学Sophie Ugolini、Guillaume Hoeffel等研究人员合作发现，感觉神经元产生的TAFA4促进巨噬细胞的组织修复功能。相关论文于2021年5月19日在线发表于国际学术期刊《自然》。

研究人员证明了感觉神经元在促进巨噬细胞组织修复功能中的主要作用。在小鼠皮肤损伤的晒斑状模型中，表达Gα_i相互作用蛋白（GINIP）的感觉神经元的条件敲除导致组织再生不良和皮肤纤维化。对潜在分子机制的阐明揭示了神经肽TAFA4的关键作用，TAFA4是由C-低阈值机械感受器（GINIP⁺神经元的一个亚群）在皮肤中产生的。TAFA4直接在体外调节巨噬细胞的炎症。

在Tafa4缺陷型小鼠中的体内研究表明，TAFA4在紫外线诱导的皮肤损伤后促进皮肤巨噬细胞产生IL-10。TAFA4-IL-10信号轴也可确保IL-10⁺TIM4⁺真皮巨噬细胞的存活和维持，减少皮肤炎症并促进组织再生。这些结果揭示了由神经肽TAFA4驱动的神经免疫调节通路，该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，并可能为炎性疾病带来新的治疗前景。

据悉，炎症是对组织损伤的防御反应，需要严密调节来防止愈合受损。驻留在组织中的巨噬细胞在组织修复中起着关键作用，但是在愈合过程中调节炎症和修复前巨噬细胞反应之间平衡的精确分子机制仍然知之甚少。

附：英文原文

Title: Sensory neuron-derived TAFA4 promotes macrophage tissue repair functions

Author: Guillaume Hoeffel, Guilhaume Debroas, Anais Roger, Rafaelle Rossignol, Jordi Gouilly, Caroline Laprie, Lionel Chasson, Pierre-Vincent Barbon, Anas Balsamo, Ana Reynders, Aziz Moqrich, Sophie Ugolini

Issue&Volume: 2021-05-19

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 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 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.

DOI: 10.1038/s41586-021-03563-7

Source: https://www.nature.com/articles/s41586-021-03563-7

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