Unbiased transcriptomic analyses reveal distinct effects of immune deficiency in CNS function with and without injury.
Unbiased transcriptomic analyses reveal distinct effects of immune deficiency in CNS function with and without injury.
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无偏见的转录组分析揭示了免疫缺陷对有损伤和无损伤的中枢神经系统功能的明显影响
DOI：
10.1007/s13238-018-0559-y
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发表时间：
2019-08
期刊：
影响因子：
21.1
通讯作者：
Cheng L
中科院分区：
文献类型：
--
作者：
Luo D;Ge W;Hu X;Li C;Lee CM;Zhou L;Wu Z;Yu J;Lin S;Yu J;Xu W;Chen L;Zhang C;Jiang K;Zhu X;Li H;Gao X;Geng Y;Jing B;Wang Z;Zheng C;Zhu R;Yan Q;Lin Q;Ye K;Sun YE;Cheng L
哺乳动物的中枢神经系统(CNS)被血脑屏障(BBB)与外周隔开，被认为是一个免疫特权系统。然而，免疫功能被认为在很大程度上影响中枢神经系统的功能状态，特别是在损伤后或神经变性期间。关于获得性免疫反应对中枢神经系统损伤修复是有利还是有害存在争议。在这项研究中，我们利用免疫低下的SCID小鼠，并使它们遭受脊髓损伤(SCI)。我们分析了运动功能、电生理学、组织化学，并进行了无偏的RNA测序。与WT小鼠相比，SCID小鼠在脊髓损伤后表现出更好的中枢功能恢复。脊髓转录的加权基因共表达网络分析(WGCNA)显示，SCID小鼠脊髓损伤后免疫功能相关基因表达减少，神经传递相关基因表达增强，免疫组织化学分析证实了这一点，并与功能恢复情况相一致。转录分析还表明，SCID小鼠在受伤前神经传递相关基因的表达增加，表明免疫缺陷的稳定状态可能导致中枢神经系统的高连接性。因此，未损伤的SCID小鼠在Morris水迷宫测试中表现出较差的表现。总而言之，不仅减少了损伤后的炎症，而且在没有损伤的情况下抑制了稳态免疫功能，提高了神经传递程序，分别导致了更好的行为结果或更差的行为结果。这项研究揭示了免疫和神经系统之间的复杂关系，为通过免疫调节治疗神经功能提供了可能性。
The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.
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WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
精神分裂症中局部和远程功能连通密度的异常模式。
影响因子：
--
作者：
Liu C;Zhang W;Chen G;Tian H;Li J;Qu H;Cheng L;Zhu J;Zhuo C
通讯作者：
Zhuo C
影响因子：
64.8
作者：
Filiano AJ;Xu Y;Tustison NJ;Marsh RL;Baker W;Smirnov I;Overall CC;Gadani SP;Turner SD;Weng Z;Peerzade SN;Chen H;Lee KS;Scott MM;Beenhakker MP;Litvak V;Kipnis J
通讯作者：
Kipnis J
牙本质基质蛋白 1 的糖基化是星形胶质细胞成熟和 BBB 完整性的新关键元素
影响因子：
21.1
作者：
Jing B;Zhang C;Liu X;Zhou L;Liu J;Yao Y;Yu J;Weng Y;Pan M;Liu J;Wang Z;Sun Y;Sun YE
通讯作者：
Sun YE
影响因子：
64.5
作者：
Lu P;Wang Y;Graham L;McHale K;Gao M;Wu D;Brock J;Blesch A;Rosenzweig ES;Havton LA;Zheng B;Conner JM;Marsala M;Tuszynski MH
通讯作者：
Tuszynski MH