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Nature：星形胶质细胞诱导的中枢神经系统炎症与肠道微生物有关！

2021-01-30 张佳兴 生物探索

星形胶质细胞肠道微生物中枢神经系统炎症
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星形胶质细胞是中枢神经系统中的丰富细胞，在神经元代谢相关的发育和体内稳态中具有调节神经活动、突触形成、限制胶质细胞维护血脑屏障等作用，这些稳态机制的失调是多种神经系统疾病的重要发病机制。

星形胶质细胞是中枢神经系统中的丰富细胞，在神经元代谢相关的发育和体内稳态中具有调节神经活动、突触形成、限制胶质细胞维护血脑屏障等作用，这些稳态机制的失调是多种神经系统疾病的重要发病机制。此外，星形胶质细胞还具有促进和扩大中枢神经系统病理反应的功能，例如神经毒性以及激活小胶质细胞和募集周围促炎细胞的能力。当前，人们对于星形胶质细胞的稳态抗炎活性及其调控机制仍然知之甚少。

《Nature》杂志在线发表了美国哈佛医学院Francisco J. Quintana团队名为“Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes”的研究。小鼠实验证明，LAMP1+TRAIL+星形胶质细胞通过诱导T细胞凋亡来限制中枢神经系统（CNS）炎症，该途径由脑膜IFNγ+ NK细胞维持，并受到肠道微生物的调节。

为了鉴定新的星形胶质细胞亚群，研究人员使用流式细胞术检测了266个抗体与小鼠星形胶质细胞的结合。他们发现，脊髓星形胶质细胞表达最丰富的标记物为溶酶体相关膜蛋白1 (LAMP1，也被称为CD107a)。并且，脊髓星形胶质细胞在实验性自身免疫性脑脊髓炎(EAE)小鼠上调，而小脑、皮质或皮质下实质星形胶质细胞均未上调。

EAE中星形胶质细胞表面标记分析

LAMP1是一种溶酶体蛋白，可在细胞膜中检测到，并与细胞毒性活性有关。研究人员使用慢病毒灭活星形胶质细胞中的LAMP1，发现CNS中表达IFN-γ和/或白介素17（IL-17）的CD4+T细胞数量增加，星形胶质细胞的促炎途径激活。但此处理并未影响CD8+T细胞以及FOXP3+Treg细胞。

星形胶质细胞中LAMP1和Tnfsf10水平

研究人员使用RNA-seq分析发现，星形胶质细胞中Lamp1的失活降低了肿瘤坏死因子（TNF）相关凋亡诱导配体TRAIL在体内的表面表达，而TRAIL和TNF家族的其他成员往往通过诱导凋亡来调节免疫反应。与这些发现一致的是，敲除Tnfsf10（TRAIL编码基因）激活了星形胶质细胞的促炎症通路。

星形胶质细胞中炎症通路

进一步研究表明，LAMP1+TRAIL+ 星形胶质细胞通过TRAIL-DR5信号传导诱导T细胞凋亡，从而限制了中枢神经系统的炎症。在体内平衡时，星形胶质细胞杀伤细胞中的干扰素-γ（IFNγ）受到肠道微生物的调节，并驱动星形胶质细胞中TRAIL的表达。在炎症形成时，T细胞和小胶质细胞产生的分子抑制星形胶质细胞中的TRAIL表达。

NK细胞抑制TRAIL表达

总而言之，LAMP1+TRAIL+星形胶质细胞通过诱导T细胞凋亡来限制CNS中枢神经系统（CNS）炎症，该途径由脑膜IFNγ+ NK细胞维持，并受到肠道微生物的调节。此研究表明了星形胶质细胞在CNS 炎症中的重要作用，也指出了肠道微生物在此途径中的调节作用。或许今后肠道微生物研究将成为CNS炎症治疗的新希望。

原始出处：

Liliana M Sanmarco 1, Michael A Wheeler 1 2, Cristina Gutiérrez-Vázquez 1, et al.Gut-licensed IFNγ + NK cells drive LAMP1 + TRAIL + anti-inflammatory astrocytes.Nature. 2021 Jan 6. doi: 10.1038/s41586-020-03116-4.

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    2021-05-08 liye789132251

    #Nat#

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    2021-10-07 wjcjjian

    #微生物#

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    #神经系统#

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    2021-02-01 bbwuyu_003

    #星形胶质细胞#

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    2021-02-01 ms1692212821629096

    #胶质细胞#

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    2021-02-01 smlt2015

    #中枢神经#

    0

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