A single-cell atlas reveals the heterogeneity of meningeal immunity in a mouse model of Methyl CpG binding protein 2 deficiency
Methyl CpG binding protein 2 (MeCP2) is a DNA methylation reader protein. Mutations in 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 deteri...
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Published in | Frontiers in immunology Vol. 13; p. 1056447 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
10.01.2023
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Subjects | |
Online Access | Get full text |
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Summary: | Methyl CpG binding protein 2 (MeCP2) is a DNA methylation reader protein. Mutations in
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 within the CNS and influence various brain functions; however, the characterization and role of meningeal immunity in CNS with MeCP2 deficiency remain poorly addressed. Here, we used single-cell sequencing to profile Mecp2-deficient meningeal immune cells from the dura mater, which has been reported to contain the most meningeal immune cells during homeostasis. Data showed that the meninges of
-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 greater in
-null mice than in control mice, and the expression of genes encoding for immunoglobulins was remarkably higher. Mecp2-deficient meninges also contained more cytotoxic CD8
T cells than control meninges. With increased interferon-γ transcription in T and natural killer cells, meningeal macrophages showed decreased suppression and increased activity in Mecp2-deficienct mice. Together, these findings provide novel insights into meningeal immunity, which is a less studied aspect of neuroimmune interactions in
-mutated diseases, and offer an essential resource for comparative analyses and data exploration to better understand the functional role of meningeal immunity in RTT. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Yunzhong Cheng, Department of Orthopedic Surgery, Capital Medical University, China; Jinming Han, Capital Medical University, China Edited by: Bo Li, Department of Orthopedics, Sun Yat-sen University, China This article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Immunology |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2022.1056447 |