MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α-PU.1 pathway.
MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α-PU.1 pathway.
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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 CD45low, major histocompatibility complex (MHC) class IIlow 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.
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影响因子：
64.8
作者：
Cullen, Bryan R.
通讯作者：
Cullen, Bryan R.
影响因子：
--
作者：
Nakamachi, Yuji;Kawano, Seiji;Kumagai, Shunichi
通讯作者：
Kumagai, Shunichi
影响因子：
64.8
作者：
Johnnidis, Jonathan B.;Harris, Marian H.;Camargo, Fernando D.
通讯作者：
Camargo, Fernando D.
影响因子：
15.3
作者：
Celada, A;Borras, FE;Maki, RA
通讯作者：
Maki, RA
DOI：
10.1073/pnas.0711961105
发表时间：
2008-04-22
影响因子：
11.1
作者：
Feng, Ru;Desbordes, Sabrina C.;Graf, Thomas
通讯作者：
Graf, Thomas