A single-cell atlas reveals heterogeneity of meningeal immunity in a mouse model of Methyl CpG binding protein 2 deficiency

ABSTRACT: Methyl CpG binding protein 2 (MeCP2) is a DNA methylation reader protein, and mutations in MeCP2 are the major cause of Rett syndrome (RTT). Increasing evidence has shown that dysregulated immunity and chronic subclinical inflammation are linked to MeCP2 deficiency and contribute to RTT development and deterioration. The meninges surrounding the central nervous system (CNS) contain a wide repertoire of immune cells that participate in immune surveillance of the CNS and influence brain functions. However, the characterization and role of meningeal immunity in CNSs with MeCP2 deficiency remain poorly understood. We applied a single-cell sequence to profile Mecp2 deficient meningeal immune cells from the dura mater, which has been reported to have the most numerous meningeal immune cells in homeostasis. The data showed that the meninges of Mecp2-null mice contained the same diverse immune cell populations as control mice and showed an up-regulation of immune-related processes. B cell populations were great larger in Mecp2-null mice than in control mice, and the expression of genes coding for immune globulins was remarkably higher. For T cells, Mecp2 deficient meninges were more enriched in cytotoxic CD8+ T cells than in the control. With increased interferon-γ transcription in T and natural killer cells, meningeal macrophages showed less suppression and were more active in Mecp2 deficiency mice. Our study provides novel insights into meningeal immunity, which is a less studied aspect of neuroimmune interactions in Mecp2 mutated diseases and offers an essential resource for comparative analyses and data exploration for a better understanding of the functional role of meningeal immunity in RTT.

ORGANISM(S): Mus musculus

PROVIDER: GSE221361 | GEO | 2022/12/29

REPOSITORIES: GEO