The role of meningeal populations of type II innate lymphoid cells in modulating neuroinflammation in neurodegenerative diseases

Abstract

Neuroinflammation: Key role for lymphatic cells Certain cells in the meningeal membranes around the brain appear to mediate inflammation of the CNS during neurodegenerative diseases. Type-II innate lymphoid cells (ILC2) reside in the lymphatic vessels in these membranes, which are increasingly recognized as important immune sites. Raymond Chuen-Chung Chang at the University of Hong Kong and co-workers reviewed studies of the distribution and activity of ILC2 in the CNS and its surroundings. They highlight promising evidence that ILC2 can modulate inflammatory triggers. There is still limited understanding of how ILC2 populations respond to damage within the brain, and limited methods for isolating and manipulating ILC2 populations. Future studies should investigate how ILC2 cells interact with inflammatory proteins, and how they could be exploited to treat brain inflammation, a common factor in neurodegenerative diseases including Alzheimer's, Parkinson's, and MS. 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, TNF alpha, 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.