Increasing evidence has challenged the traditional view about the immune privilege of the brain, but the precise roles of immune cells in regulating brain physiology and function remain poorly understood. Here, we report that tissue-resident group 2 innate lymphoid cells (ILC2) accumulate in the choroid plexus of aged brains. ILC2 in the aged brain are long-lived, are relatively resistant to cellular senescence and exhaustion, and are capable of switching between cell cycle dormancy and proliferation. They are functionally quiescent at homeostasis but can be activated by IL-33 to produce large amounts of type 2 cytokines and other effector molecules in vitro and in vivo. Intracerebroventricular transfer of activated ILC2 revitalized the aged brain and enhanced the cognitive function of aged mice. Administration of IL-5, a major ILC2 product, was sufficient to repress aging-associated neuroinflammation and alleviate aging-associated cognitive decline. Targeting ILC2 in the aged brain may provide new avenues to combat aging-associated neurodegenerative disorders.

中文翻译：

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第 2 组先天淋巴细胞的激活可缓解与衰老相关的认知能力下降

越来越多的证据挑战了关于大脑免疫特权的传统观点，但免疫细胞在调节大脑生理和功能中的确切作用仍然知之甚少。在这里，我们报告组织驻留的第 2 组先天淋巴细胞 (ILC2) 在老年大脑的脉络丛中积聚。衰老大脑中的ILC2寿命较长，对细胞衰老和耗竭具有相对抵抗力，并且能够在细胞周期休眠和增殖之间切换。它们在稳态时功能上处于静止状态，但可以被 IL-33 激活，在体外和体内产生大量 2 型细胞因子和其他效应分子。脑室内转移活化的ILC2可以使衰老的大脑恢复活力，并增强老年小鼠的认知功能。IL-5（ILC2 的主要产物）的给药足以抑制与衰老相关的神经炎症并缓解与衰老相关的认知能力下降。靶向老年大脑中的 ILC2 可能为对抗与衰老相关的神经退行性疾病提供新途径。