Mecp2 Deficiency Alters M1/M2 Gene Expresion in Bone Marrow-Derived Macrophages Upon Stimulation

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Abstract
Rett Syndrome (RTT) is a neurodevelopmental disorder mostly caused by mutations in the X-linked gene, MeCP2, which encodes for methyl-CpG binding protein 2 (MeCP2). MeCP2 is member of a family of methyl binding proteins that control the expression of several genes according to the genomic context. Emerging evidence suggests that immune dysfunctions would actively contribute to the pathogenesis of RTT. Macrophages are key effector cells that participate in several critical aspects of immune responses. The aim of our work was to assess the response of macrophages in vitro in the context of polarizing stimuli. We used bone marrow-derived macrophages (BMDM) obtained from MeCP2 308/y mice, a mouse model that carries a truncated form of MeCP2. Since MeCP2 is expressed as a “partially functional” protein in humans with RTT it becomes crucial to establish how the presence of a mutant form of MeCP2 affects immune responses to support the normal homeostasis of individuals. MeCP2 deficiency induced exacerbation of pro-inflammatory mediators and deficient immune regulatory responses under polarizing conditions. These findings suggest that MeCP2 plays a role in the establishment of macrophage polarization in the context of immune activation. Present results may have important implications in understanding RTT pathogenesis and for developing potential treatments. Conflict of interest: The authors declare no conflicts of interest.

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