Distinctive waves of innate immune response in the retina in experimental autoimmune encephalomyelitis.
Distinctive waves of innate immune response in the retina in experimental autoimmune encephalomyelitis.
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实验性自身免疫性脑脊髓炎视网膜天然免疫反应的独特波。
DOI：
10.1172/jci.insight.149228
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发表时间：
2021-06-08
期刊：
影响因子：
8
通讯作者：
Green AJ
中科院分区：
文献类型：
--
作者：
Cruz-Herranz A;Oertel FC;Kim K;Cantó E;Timmons G;Sin JH;Devereux M;Baker N;Michel B;Schubert RD;Rani L;Cordano C;Baranzini SE;Green AJ
神经变性介导CNS炎性脱髓鞘疾病的神经功能障碍。先天免疫细胞在介导这种损伤中的作用仍然存在争议，有证据表明其具有破坏性和保护性作用。这使得开发治疗方法的努力变得复杂。相反的功能的时间顺序和动态演变尤其不清楚。鉴于人类疾病如多发性硬化症（MS）的体内监测的限制，动物模型有必要研究先天免疫激活与神经变性的关联和时间。在CX 3CR 1GFP/+基因敲入小鼠中使用实验性自身免疫性脑炎（EAE）的非侵入性体内视网膜成像，随后进行转录谱分析，我们能够显示由先天免疫细胞数量的显著减少和细胞形态的变化分离的2个不同的波。第一波的特征是EAE发作前的炎症吞噬表型，而第二波的特征是慢性阶段的调节性抗炎表型。此外，第一波的幅度与神经元损失有关。发现的两种转录物-生长抑制特异性蛋白6（GAS 6）和细胞因子信号转导抑制因子3（SOCS 3）-可能是增强小胶质细胞在初始损伤后慢性期保护作用的有希望的靶点。
Neurodegeneration mediates neurological disability in inflammatory demyelinating diseases of the CNS. The role of innate immune cells in mediating this damage has remained controversial with evidence for destructive and protective effects. This has complicated efforts to develop treatment. The time sequence and dynamic evolution of the opposing functions are especially unclear. Given limits of in vivo monitoring in human diseases such as multiple sclerosis (MS), animal models are warranted to investigate the association and timing of innate immune activation with neurodegeneration. Using noninvasive in vivo retinal imaging of experimental autoimmune encephalitis (EAE) in CX3CR1GFP/+–knock-in mice followed by transcriptional profiling, we are able to show 2 distinct waves separated by a marked reduction in the number of innate immune cells and change in cell morphology. The first wave is characterized by an inflammatory phagocytic phenotype preceding the onset of EAE, whereas the second wave is characterized by a regulatory, antiinflammatory phenotype during the chronic stage. Additionally, the magnitude of the first wave is associated with neuronal loss. Two transcripts identified — growth arrest–specific protein 6 (GAS6) and suppressor of cytokine signaling 3 (SOCS3) — might be promising targets for enhancing protective effects of microglia in the chronic phase after initial injury.
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影响因子：
6.2
作者：
Halleskog C;Mulder J;Dahlström J;Mackie K;Hortobágyi T;Tanila H;Kumar Puli L;Färber K;Harkany T;Schulte G
通讯作者：
Schulte G
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR
影响因子：
9.3
作者：
Hecker, Christina;Dietrich, Michael;Albrecht, Philipp
通讯作者：
Albrecht, Philipp
影响因子：
8.8
作者：
Albrecht, Nicholas E.;Alevy, Jonathan;Samuel, Melanie A.
通讯作者：
Samuel, Melanie A.
影响因子：
9.9
作者：
Cruz-Herranz A;Balk LJ;Oberwahrenbrock T;Saidha S;Martinez-Lapiscina EH;Lagreze WA;Schuman JS;Villoslada P;Calabresi P;Balcer L;Petzold A;Green AJ;Paul F;Brandt AU;Albrecht P;IMSVISUAL consortium
通讯作者：
IMSVISUAL consortium