Choroid Plexus Fibroblast-ILC2 Niche Promotes Adult Hippocampal Neurogenesis after Traumatic Brain Injury.

Abstract

Mounting evidence has indicated that immune signals originating from the brain's border tissues will exert a profound influence on brain parenchyma neural cells. However,  the structural component alterations and immune cell infiltration characteristics of choroid plexus (ChP) following traumatic brain injury (TBI) remain incompletely understood. Here, using single-cell RNA sequencing and histological analysis, the accumulation of group 2 innate lymphoid cell (ILC2) in the ChP stroma post-TBI is identified. Intracerebroventricular adoptive transfer of ILC2 is further indicated to exhibit a tendency to colonize the ChP and significantly alleviate pathogenic immune infiltration during the acute phase of TBI, as well as maintain hippocampal integrity during the chronic phase. Sensory-motor function and memory impairments in TBI mice are also improved under ILC2 treatment. Mechanistically, ILC2 is induced by ChP fibroblasts derived IL33 and anchored to stroma fibroblasts via the VCAM-1/Integrin α4β7 pathway. Furthermore, single-nucleus RNA sequencing of the hippocampus reveals that ILC2-derived AREG promotes the initiation of neurogenesis by interacting with EGFR on early-stage neurogenic cells. Overall, these findings highlight that ChP-resident ILC2, through optimizing the immune microenvironment and promoting neurogenesis after TBI, may represent a potential therapeutic strategy.