Regulation of progenitor cell proliferation and granulocyte function by microRNA-223
Abstract
MicroRNAs are abundant in animal genomes and have been predicted to have important roles in a broad range of gene expression programmes. Despite this prominence, there is a dearth of functional knowledge regarding individual mammalian microRNAs. Using a loss-of-function allele in mice, we report here that the myeloid-specific microRNA-223 (miR-223) negatively regulates progenitor proliferation and granulocyte differentiation and activation. miR-223 (also called Mirn223) mutant mice have an expanded granulocytic compartment resulting from a cell-autonomous increase in the number of granulocyte progenitors. We show that Mef2c, a transcription factor that promotes myeloid progenitor proliferation, is a target of miR-223, and that genetic ablation of Mef2c suppresses progenitor expansion and corrects the neutrophilic phenotype in miR-223 null mice. In addition, granulocytes lacking miR-223 are hypermature, hypersensitive to activating stimuli and display increased fungicidal activity. As a consequence of this neutrophil hyperactivity, miR-223 mutant mice spontaneously develop inflammatory lung pathology and exhibit exaggerated tissue destruction after endotoxin challenge. Our data support a model in which miR-223 acts as a fine-tuner of granulocyte production and the inflammatory response.
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miR-223 is expressed in peripheral macrophages but not in microglia.
“whereas myeloid-specific miR-223 (refs. 6,22) was expressed in the macrophages in the periphery, but not in the microglia (Fig. 1b).”
From MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α–PU.1 pathway (2011) · cites this paper as [6]
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- Authors
- Johnnidis, J. B., Harris, M. H., Wheeler, R. T., Stehling-Sun, S., Lam, M. H., Kirak, O., Brummelkamp, T. R., Fleming, M. D., & Camargo, F. D.
- Venue
- Nature
- Published
- 2008-02
- Volume
- 451
- Issue
- 7182
- Pages
- 1125-1129
- ISSN
- 0028-0836
- 1476-4687
- Cited by
- 1,062
- References
- 2
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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