The interweaved signatures of common-gamma-chain cytokines across immunologic lineages

"?c" cytokines are a family whose receptors share a “common gamma chain” signaling moiety, and play central roles in the differentiation, homeostasis and communications of all immunocyte lineages. As a resource to better understand their range and specificity of action, we profiled by RNAseq the immediate-early responses to the main ?c cytokines, across all immunocyte lineages. The results show a different response landscape than expected: broader, with a strong Myc-controlled resetting of biosynthetic and metabolic pathways, a major downregulation component, and extensive overlap between cytokines (one cytokine doing in one cell what another does elsewhere). Various mechanisms appear involved: fast transcriptional activation, chromatin remodeling, and mRNA destabilization. Other surprises are uncovered: IL2 effects in mast cells, major shifts between follicular and marginal-zone B cells, paradoxical and cell-specific cross-talk between IFN and ?c signaling, or an NK-T like program induced by IL21 in CD8+ T cells. Overall design: Two replicates of follicular B cell samples, PBS-treated control and IL4-treated, underwent CUT&RUN to analyze the following targets: IgG, H3K4me1, H3K4me3, H3K27me3, H3K36me3, H3K27ac, and H3.3.