- Baysoy, Alev;
- Seddu, Kumba;
- Salloum, Tamara;
- Dawson, Caleb A;
- Lee, Juliana J;
- Yang, Liang;
- Gal-oz, Shani;
- Ner-Gaon, Hadas;
- Tellier, Julie;
- Millan, Alberto;
- Sasse, Alexander;
- Brown, Brian;
- Lanier, Lewis L;
- Shay, Tal;
- Nutt, Stephen;
- Dwyer, Daniel;
- Benoist, Christophe;
- Consortium, The Immunological Genome Project
"γc" cytokines are a family whose receptors share a "common-gamma-chain" signaling moiety, and play central roles in 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 γc cytokines across all immunocyte lineages. The results reveal an unprecedented landscape: broader, with extensive overlap between cytokines (one cytokine doing in one cell what another does elsewhere) and essentially no effects unique to any one cytokine. Responses include a major downregulation component and a broad Myc-controlled resetting of biosynthetic and metabolic pathways. Various mechanisms appear involved: fast transcriptional activation, chromatin remodeling, and mRNA destabilization. Other surprises were uncovered: IL2 effects in mast cells, shifts between follicular and marginal zone B cells, paradoxical and cell-specific cross-talk between interferon and γc signatures, or an NKT-like program induced by IL21 in CD8+ T cells.