IL-13 Ameliorates Neuroinflammation and Promotes Functional Recovery after Traumatic Brain Injury
IL-13 Ameliorates Neuroinflammation and Promotes Functional Recovery after Traumatic Brain Injury
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IL-13 可改善神经炎症并促进脑外伤后的功能恢复
DOI：
10.4049/jimmunol.1900909
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发表时间：
2020-03-15
影响因子：
4.4
通讯作者：
Gao, Yanqin
中科院分区：
文献类型：
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作者：
Miao, Wanying;Zhao, Yongfang;Gao, Yanqin
关键点IL-13改善创伤性脑损伤后的神经功能结局。IL-13调节小胶质细胞/巨噬细胞表型并抑制炎症反应。IL-13增强小胶质细胞/巨噬细胞吞噬活性。小胶质细胞在创伤性脑损伤（TBI）后的神经炎症反应中起重要作用。我们以前的研究表明，小胶质细胞的表型，以及浸润的巨噬细胞，在CNS损伤后的不同阶段发生变化，这与功能的结果。IL-13是一种抗炎细胞因子，据报道其通过免疫调节防止脱髓鞘和脊髓损伤。IL-13在TBI后小胶质细胞/巨噬细胞介导的免疫应答中的作用仍然未知。在这项研究中，我们表明，鼻内给药的IL-13在雄性C57 BL/6 J小鼠加速功能恢复的控制皮质撞击模型的TBI。IL-13治疗增加了旋转棒测试中的脱落时间，减少了足部错误测试中的足部错误数量，并在TBI后28天内改善了钢丝悬挂测试中的评分。与功能改善一致，IL-13减少了TBI后6天的神经元组织损失并保持了白色物质的完整性。此外，IL-13改善了促炎因子的升高，并减少了促炎小胶质细胞/巨噬细胞的数量。此外，IL-13增强了损伤周围区域中受损神经元的小胶质细胞/巨噬细胞吞噬作用。体外研究证实，IL-13处理抑制了大鼠原代小胶质细胞中响应于LPS或死亡神经元刺激的促炎细胞因子的产生，并增加了小胶质细胞吞噬荧光团标记的乳胶珠或死亡神经元的能力。总的来说，我们证明了IL-13治疗通过调节小胶质细胞/巨噬细胞表型和抑制炎症反应改善了TBI后的神经功能结局。IL-13可能是促进TBI长期恢复的潜在免疫疗法。
Key Points IL-13 improves neurologic outcomes after traumatic brain injury. IL-13 adjusts microglia/macrophage phenotypes and inhibits inflammatory responses. IL-13 enhances microglia/macrophage phagocytic activities. Microglia play essential roles in neuroinflammatory responses after traumatic brain injury (TBI). Our previous studies showed that phenotypes of microglia, as well as infiltrating macrophages, altered at different stages after CNS injury, which was correlated to functional outcomes. IL-13 is an anti-inflammatory cytokine that has been reported to protect against demyelination and spinal cord injury through immunomodulation. The effects of IL-13 in microglia/macrophage–mediated immune responses after TBI remain unknown. In this study, we showed that intranasal administration of IL-13 in male C57BL/6J mice accelerated functional recovery in the controlled cortical impact model of TBI. IL-13 treatment increased the time to fall off in the Rotarod test, reduced the number of foot faults in the foot fault test, and improved the score in the wire hang test up to 28 d after TBI. Consistent with functional improvement, IL-13 reduced neuronal tissue loss and preserved white matter integrity 6 d after TBI. Furthermore, IL-13 ameliorated the elevation of proinflammatory factors and reduced the number of proinflammatory microglia/macrophages 6 d after TBI. Additionally, IL-13 enhanced microglia/macrophage phagocytosis of damaged neurons in the peri-lesion areas. In vitro studies confirmed that IL-13 treatment inhibited the production of proinflammatory cytokines in rat primary microglia in response to LPS or dead neuron stimulation and increased the ability of microglia to engulf fluorophore-labeled latex beads or dead neurons. Collectively, we demonstrated that IL-13 treatment improved neurologic outcomes after TBI through adjusting microglia/macrophage phenotypes and inhibiting inflammatory responses. IL-13 may represent a potential immunotherapy to promote long-term recovery from TBI.