A novel systems immunology approach identifies the collective impact of five miRNAs in Th2 inflammation (mRNA)

Allergic asthma is a chronic inflammatory disease dominated by a CD4+ T helper 2 (Th2) cell signature. The immune response amplifies in self-enforcing loops, promoting Th2-driven cellular immunity and leaving the host unable to terminate inflammation. Posttranscriptional mechanisms, including miRNAs, are pivotal in maintaining immune-homeostasis. Since an altered expression of various miRNAs has been associated with T cell-driven diseases, including asthma, we hypothesized that miRNAs control mechanisms ensuring Th2 stability and maintenance in the lung. We isolated murine CD4+ Th2 cells from allergic inflamed lungs and profiled gene and microRNA expression. Tissue resident Th2 cells were isolated at two stages of Ovalbumin-induced allergic airway inflammation from lung tissue for RNA extraction and hybridization on Affymetrix microarrays. We obtained live cells by fluorescent-activated cells sorting based on surface marker expression at different stages: antigen-naive CD4+ T cells from spleens of sham-treated mice, Th2 cells after polarization and recruitment to the inflamed tissue (early Th2), and cells from chronic inflamed tissue (stable Th2). We sought to decipher mechanisms regulating the persistence of chronic allergic inflammation.