Immuno-genomic effects of JAK blockade in vivo. Mus musculus

Small molecule inhibitors of JAK kinases have shown clinical effcacy in the treatment of certain autoimmune diseases. While these are known to block upstream JAK signalling events, their broader impact on the transcriptional footprint in immunocytes are unknown. Here we explore the effects of pan- and isoform-specific JAK blockade on the immuno-genomic network by genomic profiling. Overall design: 6week old male C57BL/6 mice were gavaged with JAK inhibitor or vehicle for indicated treatment periods. Spleens were harvested and mechanically disrupted to prepare single cell suspensions. These were then stained in multiple surface marker panels to differentiate distinct immunocyte populations. Cells were sorted directly into TriZol. RNA was prepared in Trizol for gene expression profiling by Affymetrix Mouse Gene 1.0 ST Arrays.