Whole lung transcriptomics of a house dust mite/cyclic di-GMP model of severe asthma

Purpose: Identify whole lung gene expression patterns in a house dust mite model of severe asthma Methods: Lung gene expression profiles of 10 week old BALB/c female mice were generated by ribosome-depleted, 100 nt, paired-end, stranded RNA-seq with Illumina HiSeq v4. Sequence reads were analyzed with Sailfish-cir to identify linear RNA transcripts and circular RNAs. Differential expression of linear RNAs was assessed with Deseq2 . QRT–PCR validation was performed using TaqMan and SYBR Green methods. Results: 100 million sequence reads per sample were mapped to the mouse genome (build mm10) using Sailfish-cir to identify linear and circular RNA transcripts. Pathway analysis of differentially expressed genes identified upregulation of gene sets for human Th17 high, Th2 low asthma. An LNA/DNA miR-155 antagonist upregulated interferon signaling pathways suggesting a general antiinflammatory effect of LNA/DNA oligos in the lung. Dexamethasone did not consistently reduce expression of Th2 or Th17 biomarker genes. Conclusions: Cyclic di-GMP plus house dust mite allergens elicited a Th2 low, Th17 high gene expression profile that was not consistently modified by treatment with dexamethasone. Overall design: Linear and circular RNA transcript expression was compared in whole lung tissue from unsensitized, house dust mite sensitzed, antimiR-155 treated and dexamethasone-treated mice