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. 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