Bridging the gap-Immune cells that can repair nerves.-猫眼课题宝

DOI：

10.1038/s41423-021-00642-7

发表时间：

2021-04

期刊：

Cellular & molecular immunology

影响因子：

24.1

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

McGettrick HM

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115059/

在一个充满病原体的世界里，免疫力是生存的关键。像大多数军事行动一样，免疫系统的策略是基于可接受的损失：确定击败或捕获任何入侵病原体所需的未感染组织的最大损伤量。这一特征对免疫介导疾病（包括许多神经系统疾病）患者具有破坏性后果。然而，自然界通常会创造一个“制衡”系统，免疫系统也不例外，它已经开发出一种修复策略来减轻白细胞对微生物的反应所造成的不必要的组织损伤。目前还不清楚这种策略是否也用于无菌损伤部位。Sas及其同事最近描述了一种新的中性粒细胞亚群，能够促进急性损伤后的神经修复。1免疫抑制性白细胞最早于1977年被描述，其中Kung证明表达精氨酸酶1（Arg 1）的骨髓细胞能够抑制细胞毒性反应。2在过去的40多年里，越来越多的证据将免疫抑制或再生特性归因于表达Arg 1和甘露糖受体（CD 206）的髓样细胞亚群，创造了交替激活细胞、非常规细胞、M2巨噬细胞和N2中性粒细胞等术语。这些细胞功能可以通过用细胞因子或生长因子极化骨髓细胞在体外复制：用IL-4或IL-13 3刺激单核细胞，用TGFβ或GM-CSF刺激中性粒细胞。4此外，已描述了这些细胞存在于伤口修复部位，例如皮肤5和脊髓6，并且这些细胞被认为是消退和修复因子（例如IL-10和TGFβ）的重要来源。促炎性白细胞浸润到中枢神经系统（CNS）中被认为在多发性硬化（MS 7）和中风的情况下是有害的。8但这只代表了故事的一半：具有M2样表型（Arg 1+）的CNS驻留巨噬细胞（小胶质细胞）存在于进入临床缓解的MS患者中。事实上，据报道，M2小胶质细胞表型的转变与鼠祖细胞分化为髓鞘形成少突胶质细胞以修复大脑中毒素诱导的脱髓鞘区域相一致。10其他研究表明，Ly 6 G+中性粒细胞而不是单核细胞的早期浸润分泌再生因子（例如，肿瘤调节蛋白10），因此是视神经再生10和脊髓修复的主要调节因子[例如，6]。尽管有这些早期的研究，我们的知识仍然存在差距，例如哪些信号促进中性粒细胞从组织损伤功能转换为组织修复功能。

Immunity is critical for survival in a world plagued by pathogens. Like that of most military operations, the strategy of the immune system is based on acceptable losses: determining the maximal amount of damage to uninfected tissues that is necessary to defeat or entrap any invading pathogen. This characteristic has devastating consequences for patients with immune-mediated diseases, including many neurological conditions. However, nature often creates a system of “checks and balances”, and the immune system is no exception, having developed a repair strategy to mitigate unwanted tissue damage resulting from leukocyte responses to microbes. It is unclear whether such strategies are also used at sites of sterile injury. Sas and colleagues recently described a novel neutrophil subpopulation that is capable of promoting nerve repair following acute injury. 1 Immunosuppressive leukocytes were first described in 1977, in which Kung demonstrated that myeloid cells expressing arginase 1 (Arg1) were capable of suppressing cytotoxic responses. 2 Over the last 40+ years, a growing body of evidence has attributed immunosuppressive or regenerative properties to subpopulations of myeloid cells that express Arg1 and the mannose receptor (CD206), coining the terms alternatively activated cells, unconventional cells, M2 macrophages and N2 neutrophils. These cellular functions can be replicated in vitro by polarizing myeloid cells with cytokines or growth factors: monocytes stimulated with IL-4 or IL-13 3 and neutrophils stimulated with TGFβ or GM-CSF. 4 Furthermore, the presence of these cells has been described at sites of wound repair, such as the skin 5 and spinal cord, 6 and these cells are thought to be an important source of resolution and reparative factors, such as IL-10 and TGFβ.The infiltration of proinflammatory leukocytes into the central nervous system (CNS) is considered detrimental in the context of multiple sclerosis (MS 7) and stroke. 8 But this represents only half of the story: CNS-resident macrophages (microglia) with an M2-like phenotype (Arg1+) are present in MS patients entering clinical remission. 9 Indeed, the switch to the M2 microglial phenotype has been reported to coincide with the differentiation of murine progenitor cells into myelin sheath-forming oligodendrocytes to repair regions of toxin-induced demyelination in the brain. 10 Other studies have suggested that it is the early infiltration of Ly6G+ neutrophils, rather than monocytes, who secrete regenerative factors (eg, oncomodulin 10) and are therefore the principal regulators of optic nerve regeneration 10 and spinal cord repair [eg, 6]. Despite these early studies, gaps in our knowledge remain, such as which signals promote neutrophils to switch from tissue-damaging to tissue-repairing functions.