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Cutting edge: microRNA regulation of macrophage fusion into multinucleated giant cells.


ABSTRACT: Cellular fusion of macrophages into multinucleated giant cells is a distinguishing feature of the granulomatous response to inflammation, infection, and foreign bodies (Kawai and Akira. 2011. Immunity 34: 637-650). We observed a marked increase in fusion of macrophages genetically deficient in Dicer, an enzyme required for canonical microRNA (miRNA) biogenesis. Gene expression profiling of miRNA-deficient macrophages revealed an upregulation of the IL-4-responsive fusion protein Tm7sf4, and analyses identified miR-7a-1 as a negative regulator of macrophage fusion, functioning by directly targeting Tm7sf4 mRNA. miR-7a-1 is itself an IL-4-responsive gene in macrophages, suggesting feedback control of cellular fusion. Collectively, these data indicate that miR-7a-1 functions to regulate IL-4-directed multinucleated giant cell formation.

SUBMITTER: Sissons JR 

PROVIDER: S-EPMC3381877 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Cutting edge: microRNA regulation of macrophage fusion into multinucleated giant cells.

Sissons James R JR   Peschon Jacques J JJ   Schmitz Frank F   Suen Rosa R   Gilchrist Mark M   Aderem Alan A  

Journal of immunology (Baltimore, Md. : 1950) 20120601 1


Cellular fusion of macrophages into multinucleated giant cells is a distinguishing feature of the granulomatous response to inflammation, infection, and foreign bodies (Kawai and Akira. 2011. Immunity 34: 637-650). We observed a marked increase in fusion of macrophages genetically deficient in Dicer, an enzyme required for canonical microRNA (miRNA) biogenesis. Gene expression profiling of miRNA-deficient macrophages revealed an upregulation of the IL-4-responsive fusion protein Tm7sf4, and anal  ...[more]

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