Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury

The meningeal space is occupied by a diverse repertoire of innate and adaptive immune cells. CNS injury elicits a rapid immune response that affects neuronal survival and recovery, but the role of meningeal inflammation in CNS injury remains poorly understood. Here we describe group 2 innate lymphoid cells (ILC2s) as a novel cell type resident in the healthy meninges that is activated following CNS injury. ILC2s are present throughout the naïve mouse meninges, though are concentrated around the dural sinuses, and have a unique transcriptional profile relative to lung ILC2s. After spinal cord injury, meningeal ILC2s are activated in an IL-33 dependent manner, producing type 2 cytokines. Using RNAseq, we characterized the gene programs that underlie the ILC2 activation state. Finally, addition of wild type lung-derived ILC2s into the meningeal space of IL-33R-/- animals improves recovery following spinal cord injury. These data characterize ILC2s as a novel meningeal cell type that responds to and functionally affects outcome after spinal cord injury, and could lead to new therapeutic insights for CNS injury or other neuroinflammatory conditions. Overall design: ILC2s were isolated from 10 week C57/Bl6 mice with and without spinal cord injury (1 day post injury). 5 mice were pooled per group, with meninges dissected, digested, and FACs sorted (CD45+/DAPI-/Lin–/St2+/Thy1+) directly into RNA lysis buffer.

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Gadani SP, Smirnov I, Smith AT, Overall CC, Kipnis J