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MeCP2 reinforces STAT3 signaling and the generation of effector CD4+ T cells by promoting miR-124-mediated suppression of SOCS5.

Publication ,  Journal Article
Jiang, S; Li, C; McRae, G; Lykken, E; Sevilla, J; Liu, S-Q; Wan, Y; Li, Q-J
Published in: Sci Signal
March 11, 2014

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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Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

March 11, 2014

Volume

7

Issue

316

Start / End Page

ra25

Location

United States

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
 

Citation

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Jiang, S., Li, C., McRae, G., Lykken, E., Sevilla, J., Liu, S.-Q., … Li, Q.-J. (2014). MeCP2 reinforces STAT3 signaling and the generation of effector CD4+ T cells by promoting miR-124-mediated suppression of SOCS5. Sci Signal, 7(316), ra25. https://doi.org/10.1126/scisignal.2004824
Jiang, Shan, Chaoran Li, Gabrielle McRae, Erik Lykken, Jose Sevilla, Si-Qi Liu, Ying Wan, and Qi-Jing Li. “MeCP2 reinforces STAT3 signaling and the generation of effector CD4+ T cells by promoting miR-124-mediated suppression of SOCS5.Sci Signal 7, no. 316 (March 11, 2014): ra25. https://doi.org/10.1126/scisignal.2004824.
Jiang S, Li C, McRae G, Lykken E, Sevilla J, Liu S-Q, et al. MeCP2 reinforces STAT3 signaling and the generation of effector CD4+ T cells by promoting miR-124-mediated suppression of SOCS5. Sci Signal. 2014 Mar 11;7(316):ra25.
Jiang, Shan, et al. “MeCP2 reinforces STAT3 signaling and the generation of effector CD4+ T cells by promoting miR-124-mediated suppression of SOCS5.Sci Signal, vol. 7, no. 316, Mar. 2014, p. ra25. Pubmed, doi:10.1126/scisignal.2004824.
Jiang S, Li C, McRae G, Lykken E, Sevilla J, Liu S-Q, Wan Y, Li Q-J. MeCP2 reinforces STAT3 signaling and the generation of effector CD4+ T cells by promoting miR-124-mediated suppression of SOCS5. Sci Signal. 2014 Mar 11;7(316):ra25.

Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

March 11, 2014

Volume

7

Issue

316

Start / End Page

ra25

Location

United States

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