Macrophage monocarboxylate transporter 1 promotes peripheral nerve regeneration after injury in mice
Macrophage monocarboxylate transporter 1 promotes peripheral nerve regeneration after injury in mice
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DOI：
10.1172/jci141964
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发表时间：
2021-11-01
影响因子：
15.9
通讯作者：
Morrison, Brett M.
中科院分区：
文献类型：
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作者：
Jha, Mithilesh Kumar;Passero, Joseph, V;Morrison, Brett M.
周围神经具有再生能力，但再生速度非常缓慢，许多神经损伤导致患者恢复不完全和永久残疾。巨噬细胞在周围神经对损伤的反应中起关键作用，有助于沃勒变性和神经再生，并且它们的功能最近已被证明依赖于细胞内代谢。迄今为止，其细胞内代谢对周围神经再生的影响尚未研究。我们研究了条件转基因小鼠与选择性消融的巨噬细胞的溶质载体家族16，成员1（Slc16a1），它编码单羧酸转运蛋白1（MCT 1），并发现，MCT 1有助于巨噬细胞的代谢，表型和功能，特别是在吞噬作用和外周神经再生。野生型巨噬细胞的连续细胞转移改善巨噬细胞选择性MCT1null小鼠受损的神经再生。我们还开发了一种在巨噬细胞中过表达MCT 1的小鼠模型，发现这些小鼠的外周神经再生速度比对照小鼠更快。我们的研究提供了进一步的证据，证明MCT 1在巨噬细胞中具有重要的生物学作用，并且操纵巨噬细胞代谢可以促进周围神经损伤的恢复，而目前尚无批准的药物治疗方法。
Peripheral nerves have the capacity for regeneration, but the rate of regeneration is so slow that many nerve injuries lead to incomplete recovery and permanent disability for patients. Macrophages play a critical role in the peripheral nerve response to injury, contributing to both Wallerian degeneration and nerve regeneration, and their function has recently been shown to be dependent on intracellular metabolism. To date, the impact of their intracellular metabolism on peripheral nerve regeneration has not been studied. We examined conditional transgenic mice with selective ablation in macrophages of solute carrier family 16, member 1 (Slc16a1), which encodes monocarboxylate transporter 1 (MCT1), and found that MCT1 contributed to macrophage metabolism, phenotype, and function, specifically in regard to phagocytosis and peripheral nerve regeneration. Adoptive cell transfer of wild-type macrophages ameliorated the impaired nerve regeneration in macrophage-selective MCT1null mice. We also developed a mouse model that overexpressed MCT1 in macrophages and found that peripheral nerves in these mice regenerated more rapidly than in control mice. Our study provides further evidence that MCT1 has an important biological role in macrophages and that manipulations of macrophage metabolism can enhance recovery from peripheral nerve injuries, for which there are currently no approved medical therapies.