Systemic sterile induced-co-expression of IL-12 and IL-18 drive IFN-γ-dependent activation of microglia and recruitment of MHC-II-expressing inflammatory monocytes into the brain.
Systemic sterile induced-co-expression of IL-12 and IL-18 drive IFN-γ-dependent activation of microglia and recruitment of MHC-II-expressing inflammatory monocytes into the brain.
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IL-12和IL-18驱动IFN-γ依赖性小胶质细胞的IL-12和IL-18驱动型诱导的无菌表达，并募集MHC-II表达炎症单核细胞到大脑中。
DOI：
10.1016/j.intimp.2022.108546
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发表时间：
2022-04
影响因子：
5.6
通讯作者：
Rodriguez-Galan MC
中科院分区：
文献类型：
--
作者：
Gaviglio EA;Peralta Ramos JM;Arroyo DS;Bussi C;Iribarren P;Rodriguez-Galan MC
神经炎症的发生以及几种神经退行性疾病的进展与全身炎症引起的外周免疫系统的激活和动员有关。然而，这种情况发生的机制仍不清楚。在这里，我们探讨了全身无菌诱导的 IL-12 和 IL-18 共表达在建立新型细胞因子介导的神经炎症模型中的作用。在 C57BL/6 小鼠中对 IL-12 加 IL-18 cDNA 进行外周流体动力剪切后，我们诱导了 IL-12 的全身和持续水平，这反过来又促进了循环促炎细胞因子 TNF-α 和 IFN-γ 的升高，并伴有脾肿大。此外，尽管我们发现大脑中 TNF-α 和 IFN-γ 的基因表达增加。我们观察到，只有 IFN-γ，而不是通过其 I 型受体的 TNF-α 信号传导，才能诱导白细胞从外周向大脑的运输，并上调小胶质细胞和炎症单核细胞中的 MHC-II。因此，只有 TNF-α 被证明是可有可无的，揭示了小胶质细胞的 IFN-γ 依赖性激活和白细胞的募集，特别是高度活化的炎症单核细胞。综上所述，我们的结果表明系统性细胞因子介导的神经炎症的建立和发展，并确定 IFN-γ 作为免疫调节的潜在靶标。
The development of neuroinflammation, as well as the progression of several neurodegenerative diseases, has been associated with the activation and mobilization of the peripheral immune system due to systemic inflammation. However, the mechanism by which this occurs remains unclear. Here, we addressed the effect of systemic sterile induced-co-expression of IL-12 and IL-18, in the establishment of a novel cytokine-mediated model of neuroinflammation. Following peripheral hydrodynamic shear of IL-12 plus IL-18 cDNAs in C57BL/6 mice, we induced systemic and persistent level of IL-12, which in turn promoted the elevation of circulating pro-inflammatory cytokines TNF-α and IFN-γ, accompanied with splenomegaly. Moreover, even though we identified an increased gene expression of both TNF-α and IFN-γ in the brain. We observed that only IFN-γ, but not TNF-α signaling through its type I receptor, was required to induce both the trafficking of leukocytes from the periphery toward the brain and upregulate MHC-II in microglia and inflammatory monocytes. Therefore, only TNF-α was shown to be dispensable, revealing an IFN-γ-dependent activation of microglia and recruitment of leukocytes, particularly of highly activated inflammatory monocytes. Taken together, our results argue for a systemic cytokine-mediated establishment and development of neuroinflammation, having identified IFN-γ as a potential target for immunomodulation.
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影响因子：
7.7
作者：
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通讯作者：
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影响因子：
32.4
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15.1
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通讯作者：
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