To explore the role of miRNAs in IgE-induced cardiac fibrosis, we performed unbiased miRNA deep sequencing analyses and discovered a novel signaling pathway (IgE/FcεR1/miR-486a-5p/Smad1) that acts in IgE-mediated CF activation in vitro and cardiac fibrosis in vivo. This evidence concerns the gene IGHE and cystic fibrosis.