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  • The interweaved signatures ...
    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

    The Journal of experimental medicine, 07/2023, Letnik: 220, Številka: 7
    Journal Article

    "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.