Group 2 innate lymphoid cells resolve neuroinflammation following cerebral ischaemia.

IF 4.4 1区 医学 Q1 CLINICAL NEUROLOGY
Stroke and Vascular Neurology Pub Date : 2023-10-01 Epub Date: 2023-04-18 DOI:10.1136/svn-2022-001919
Pei Zheng, Yuwhen Xiu, Zhili Chen, Meng Yuan, Yan Li, Ningning Wang, Bohao Zhang, Xin Zhao, Minshu Li, Qiang Liu, Fu-Dong Shi, Wei-Na Jin
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引用次数: 1

Abstract

Background: Acute brain ischaemia elicits pronounced inflammation, which aggravates neural injury. However, the mechanisms governing the resolution of acute neuroinflammation remain poorly understood. In contrast to regulatory T and B cells, group 2 innate lymphoid cells (ILC2s) are immunoregulatory cells that can be swiftly mobilised without antigen presentation; whether and how these ILC2s participate in central nervous system inflammation following brain ischaemia is still unknown.

Methods: Leveraging brain tissues from patients who had an ischaemic stroke and a mouse model of focal ischaemia, we characterised the presence and cytokine release of brain-infiltrating ILC2s. The impact of ILC2s on neural injury was evaluated through antibody depletion and ILC2 adoptive transfer experiments. Using Rag2-/-γc-/- mice receiving passive transfer of IL-4-/- ILC2s, we further assessed the contribution of interleukin (IL)-4, produced by ILC2s, in ischaemic brain injury.

Results: We demonstrate that ILC2s accumulate in the areas surrounding the infarct in brain tissues of patients with cerebral ischaemia, as well as in mice subjected to focal cerebral ischaemia. Oligodendrocytes were a major source of IL-33, which contributed to ILC2s mobilisation. Adoptive transfer and expansion of ILC2s reduced brain infarction. Importantly, brain-infiltrating ILC2s reduced the magnitude of stroke injury severity through the production of IL-4.

Conclusions: Our findings revealed that brain ischaemia mobilises ILC2s to curb neuroinflammation and brain injury, expanding the current understanding of inflammatory networks following stroke.

第2组先天性淋巴细胞解决脑缺血后的神经炎症。
背景:急性脑缺血引起明显的炎症,加重神经损伤。然而,控制急性神经炎症解决的机制仍知之甚少。与调节性T和B细胞相反,第2组先天性淋巴细胞(ILC2)是免疫调节细胞,可以在没有抗原呈递的情况下快速动员;这些ILC2是否以及如何参与脑缺血后的中枢神经系统炎症仍然未知。方法:利用缺血性中风患者的脑组织和局灶性缺血小鼠模型,我们表征了脑浸润性ILC2的存在和细胞因子的释放。通过抗体耗竭和ILC2过继转移实验评估了ILC2对神经损伤的影响。使用接受IL-4-/-ILC2s被动转移的Rag2-/-γc-/-小鼠,我们进一步评估了ILC2s产生的白细胞介素(IL)-4在缺血性脑损伤中的作用。结果:我们证明ILC2在脑缺血患者和局灶性脑缺血小鼠的脑组织梗死周围区域积聚。少突胶质细胞是IL-33的主要来源,它有助于ILC2的动员。ILC2的过继转移和扩增减少了脑梗死。重要的是,脑浸润性ILC2通过产生IL-4降低了中风损伤的严重程度。结论:我们的研究结果表明,脑缺血动员ILC2来抑制神经炎症和脑损伤,扩大了目前对中风后炎症网络的理解。
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来源期刊
Stroke and Vascular Neurology
Stroke and Vascular Neurology Medicine-Cardiology and Cardiovascular Medicine
CiteScore
11.20
自引率
1.70%
发文量
63
审稿时长
15 weeks
期刊介绍: Stroke and Vascular Neurology (SVN) is the official journal of the Chinese Stroke Association. Supported by a team of renowned Editors, and fully Open Access, the journal encourages debate on controversial techniques, issues on health policy and social medicine.
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