@article{f4c7758606f24725a5d4538d7413a7f2,
title = "Methyl-CpG Binding Protein 2 Regulates Microglia and Macrophage Gene Expression in Response to Inflammatory Stimuli",
abstract = "Mutations in MECP2, encoding the epigenetic regulator methyl-CpG-binding protein 2, are the predominant cause of Rett syndrome, a disease characterized by both neurological symptoms and systemic abnormalities. Microglial dysfunction is thought to contribute to disease pathogenesis, and here we found microglia become activated and subsequently lost with disease progression in Mecp2-null mice. Mecp2 was found to be expressed in peripheral macrophage and monocyte populations, several of which also became depleted in Mecp2-null mice. RNA-seq revealed increased expressionofglucocorticoid- and hypoxia-induced transcripts in Mecp2-deficient microglia and peritoneal macrophages. Furthermore, Mecp2 was found to regulate inflammatory gene transcription in response to TNF stimulation. Postnatal re-expression of Mecp2 using Cx3cr1creER increased the lifespan of otherwise Mecp2-null mice. These data suggest that Mecp2 regulates microglia and macrophage responsiveness to environmental stimuli to promote homeostasis. Dysfunction of tissue-resident macrophages might contribute to the systemic pathologies observed in Rett syndrome.",
author = "Cronk, {James C.} and Derecki, {No{\"e}l C.} and Emily Ji and Yang Xu and Lampano, {Aaron E.} and Igor Smirnov and Wendy Baker and Norris, {Geoffrey T.} and Ioana Marin and Nathan Coddington and Yochai Wolf and Turner, {Stephen D.} and Alan Aderem and Klibanov, {Alexander L.} and Harris, {Tajie H.} and Steffen Jung and Vladimir Litvak and Jonathan Kipnis",
note = "Funding Information: We thank Shirley Smith for editorial assistance and Dr. Alex Koeppel (Bioinformatics Core, School of Medicine, University of Virginia) for his initial analysis of RNA-seq data. We thank Dr. Arthur Mercurio and Bryan Pursell (Department of Molecular, Cell and Cancer Biology, UMass Medical School) for their help with hypoxia experiments. We thank the members of the Kipnis laboratory, as well as the members of the Center for Brain Immunology and Glia (BIG) for their valuable comments during multiple discussions of this work. N.C.D. was supported by Hartwell Foundation post-doctoral fellowship. J.C.C. was supported by an award from the National Institute of Allergy and Infectious Diseases 1F30AI109984. This work was primarily supported by a grant from the National Institutes of Neurological Disorders and Stroke NS081026 (J. K.), the Simons Foundation Autism Research Initiative (J. K.), and from the Rett Syndrome Research Trust (J. K.). Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = apr,
day = "21",
doi = "10.1016/j.immuni.2015.03.013",
language = "English",
volume = "42",
pages = "679--691",
journal = "Immunity",
issn = "1074-7613",
number = "4",
}