Cutting edge: microRNA regulation of macrophage fusion into multinucleated giant cells.
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.
Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
James R
JR
Sissons
Jacques J
JJ
Peschon
Frank
F
Schmitz
Rosa
R
Suen
Mark
M
Gilchrist
Alan
A
Aderem
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002459:Cell Fusion / Q000379:methods; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000235:genetics; D015744:Giant Cells, Langhans / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology; D008264:Macrophages / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D043244:Ribonuclease III / Q000172:deficiency / Q000235:genetics; D014158:Transcription, Genetic / Q000276:immunology
C501590:Dcstamp protein, mouse; C549243:MIRN7 microRNA, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; D015847:Interleukin-4; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases