Novel subsets of peripheral immune cells associated with promoting stroke recovery in mice

Abstract

Aims: Peripheral immune cells infiltrating into the brain trigger neuroinflammation after an ischemic stroke. Partial immune cells reprogram their function for neural repair. Which immune cells promote ischemic brain recovery needs further identification.

Methods: We performed single-cell transcriptomic profiling of CD45^high immune cells isolated from the ischemic hemisphere at subacute (5 days) and chronic (14 days) stages after ischemic stroke.

Results: A subset of phagocytic macrophages was associated with neuron projection regeneration and tissue remodeling. We also identified a unique type of T cells with highly expressed macrophage markers, including C1q, Apoe, Hexb, and Fcer1g, which showed high abilities in tissue remodeling, myelination regulation, wound healing, and anti-neuroinflammation. Moreover, natural killer cells decreased cytotoxicity and increased energy and metabolic function in the chronic stage after ischemic stroke. Two subgroups of neutrophils upregulated CCL signals to recruit peripheral immune cells and released CXCL2 to keep self-recruiting at the chronic stage.

Conclusions: We identified subsets of peripheral immune cells that may provide potential therapeutic targets for promoting poststroke recovery.

Keywords: brain recovery; mouse model; peripheral immune cells; single‐cell RNA sequencing; stroke.