MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α-PU.1 pathway

Eugene D. Ponomarev, Tatyana Veremeyko, Natasha Barteneva, Anna M. Krichevsky, Howard L. Weiner

Research output: Contribution to journalArticle

476 Citations (Scopus)

Abstract

MicroRNAs are a family of regulatory molecules involved in many physiological processes, including differentiation and activation of cells of the immune system. We found that brain-specific miR-124 is expressed in microglia but not in peripheral monocytes or macrophages. When overexpressed in macrophages, miR-124 directly inhibited the transcription factor CCAAT/enhancer-binding protein-α(C/EBP-α) and its downstream target PU.1, resulting in transformation of these cells from an activated phenotype into a quiescent CD45 low, major histocompatibility complex (MHC) class II low phenotype resembling resting microglia. During experimental autoimmune encephalomyelitis (EAE), miR-124 was downregulated in activated microglia. Peripheral administration of miR-124 in EAE caused systemic deactivation of macrophages, reduced activation of myelin-specific T cells and marked suppression of disease. Conversely, knockdown of miR-124 in microglia and macrophages resulted in activation of these cells in vitro and in vivo. These findings identify miR-124 both as a key regulator of microglia quiescence in the central nervous system and as a previously unknown modulator of monocyte and macrophage activation.

Original languageEnglish
Pages (from-to)64-70
Number of pages7
JournalNature Medicine
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 1 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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