Recent research into meningeal lymphatics has revealed a never-before appreciated role of type II innate lymphoid cells (ILC2s) in modulating neuroinflammation in the central nervous system (CNS). To date, the role of ILC2-mediated inflammation in the periphery has been well studied. However, the exact distribution of ILC2s in the CNS and therefore their putative role in modulating neuroinflammation in neurodegenerative diseases such as Alzheimer’s disease (AD), multiple sclerosis (MS), Parkinson’s disease (PD), and major depressive disorder (MDD) remain highly elusive. Here, we review the current evidence of ILC2-mediated modulation of neuroinflammatory cues (i.e., IL-33, IL-25, IL-5, IL-13, IL-10, TNFα, and CXCL16-CXCR6) within the CNS, highlight the distribution of ILC2s in both the periphery and CNS, and discuss some challenges associated with cell type-specific targeting that are important for therapeutics. A comprehensive understanding of the roles of ILC2s in mediating and responding to inflammatory cues may provide valuable insight into potential therapeutic strategies for many dementia-related disorders.

最近对脑膜淋巴管的研究揭示了 II 型先天性淋巴样细胞 (ILC2s) 在调节中枢神经系统 (CNS) 神经炎症方面的前所未有的作用。迄今为止，ILC2 介导的炎症在外周的作用已得到充分研究。然而，ILC2 在 CNS 中的确切分布及其在调节神经退行性疾病（如阿尔茨海默病 (AD)、多发性硬化症 (MS)、帕金森病 (PD) 和重度抑郁症 (MDD)）中的神经炎症中的推定作用仍然高度关注难以捉摸。在这里，我们回顾了 CNS 中 ILC2 介导的神经炎症信号（即 IL-33、IL-25、IL-5、IL-13、IL-10、TNFα 和 CXCL16-CXCR6）调节的当前证据，强调ILC2在外围和CNS中的分布，并讨论与对治疗很重要的细胞类型特异性靶向相关的一些挑战。全面了解 ILC2 在介导和响应炎症信号中的作用可能为许多痴呆相关疾病的潜在治疗策略提供有价值的见解。