Figure 6
The effect of bmal1 deletion in dendritic cells on circadian-gated responses to ES antigen. Bone marrow derived DCs were cultured from Bmalfl/fl and CD11c-bmal−/− mice and (A) purity confirmed by flow cytometry. After 48 h temperature synchronisation, cells were challenged for 3 h with ES antigen (or vehicle) at either the peak or trough of PER2::luc activity and RNA-Seq was performed. Data represents 3 technical repeats. Venn diagrams showing genes exhibiting significant (Padj < 0.05) diurnal variation in the two genotypes in naïve cells (B, blue) and ES stimulated cells (C, green). (D) Pathway analysis mapping differences in gene expression between Peak and Trough ES challenge in bmalfl/fl mice. Blue bars, pathways down-regulated at peak, red bars, pathways up-regulated at peak. (E) Pathway analysis mapping differences between CD11c-bmal−/− and bmalfl/fl cells after stimulation with ES antigen at the trough of PER2::luc activity. Blue bars, pathways down regulated in CD11c-bmal−/−. Red bars, pathways up-regulated in CD11c-bmal−/−. (F) Heat map showing gene expression across the treatment groups, highlighting increased induction of genes after ES stimulation in bmalfl/fl versus CD11c-bmal−/− mice at the trough of PER2::luc activity. (G) Schematic illustrating the role of time-of-day of infection on parasitic worm expulsion. See also Fig. S5 and Tables S2 and S3.
