MeCP2 reinforces STAT3 signaling and the generation of effector CD4+ T cells by promoting miR-124-mediated suppression of SOCS5.
Methyl CpG binding protein 2 (MeCP2) is an X-linked, multifunctional epigenetic regulator that is best known for its role in the neurological disorder Rett syndrome; however, it is also linked to multiple autoimmune disorders. We examined a potential role for MeCP2 in regulating the responses of CD4+ T cells to stimulation with antigen. MeCP2 was indispensable for the differentiation of naïve CD4+ T cells into T helper type 1 (T(H)1) and T(H)17 cells and for T(H)1- or T(H)17-mediated pathologies in vitro and in vivo. Loss of MeCP2 in CD4+ T cells impaired the expression of the microRNA (miR) miR-124 and consequently relieved miR-124-mediated repression of the translation of suppressor of cytokine signaling 5 (Socs5) mRNA. The resulting accumulation of SOCS5 inhibited the cytokine-dependent activation of signal transducer and activator of transcription 1 (STAT1) and STAT3, which are necessary for the differentiation of T(H)1 and T(H)17 cells, respectively. Upon silencing of MeCP2, primary neurons and astrocytes also failed to respond properly to STAT3-dependent signaling stimulated by neurotrophic factors. Together, these findings suggest that the regulation of STAT3 signaling may represent a common etiology underpinning the roles of MeCP2 in both the nervous and immune systems.
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- Suppressor of Cytokine Signaling Proteins
- Signal Transduction
- STAT3 Transcription Factor
- Quinolines
- Polymerase Chain Reaction
- Organic Chemicals
- MicroRNAs
- Mice, Knockout
- Mice
- Methyl-CpG-Binding Protein 2
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Suppressor of Cytokine Signaling Proteins
- Signal Transduction
- STAT3 Transcription Factor
- Quinolines
- Polymerase Chain Reaction
- Organic Chemicals
- MicroRNAs
- Mice, Knockout
- Mice
- Methyl-CpG-Binding Protein 2