Lower temperatures reduce type I interferon activity and promote alphaviral arthritis
Fig 6
RNA-Seq of feet of mice housed at 30°C or 22°C.
(A) Mice housed at 30°C or 22°C were injected s.c. into feet with poly(I:C)/jetPEI. After 12 hours feet were harvested, mRNA was extracted and subjected to RNA-Seq analysis. Differentially expressed genes (q<0.01, CPM>1 in at least 3 samples) were analyzed by the IPA upstream regulator (USR) function (direct only). Selected USRs associated with the type I IFN response are shown ranked by Z score. Transcription factor activities associated with enhanced type I IFN responses are colored red. Transcription factor activities associated with reduced type I IFN responses are colored green. P values are provided above/below the bars. (B) As for (a) with mice housed at 30°C or 22°C for 2 days, but with feet harvested without any treatment. (C) The raw RNA-Seq sequencing data was independently analyzed by ISMARA (full results shown in S1 Table). The transcription factor binding site (left) and site activity (right) are shown (with associated Z values) for XBP1, ATF3 and HSF1. ISMARA quantifies significance as a Z-value, with a site with a higher Z value ranked as more significant than one with a lower Z value. The activity score is an arbitrary score provided by the program and if error bars overlap significance is deemed not to have been reached [54]. The significant Expression/Activity correlations (positive for XBP1 and HSF1, and negative for ATF3) are shown in S7B Fig.