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

Abstract

“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.

Regulatory T cell-derived enkephalin gates nociception

“…This open chromatin was similar to the open chromatin, promoter and enhancer regions of the developing forebrain, an established enkephalin-producing area of the murine CNS (Figure 3C) 41 . By analyzing the raw dataset from the Immunological Genome Project 42 , we also explored Penk expression within cell populations of the immune system. We observed a strikingly greater Penk expression in Tregs, compared to other immune cells ( Figure 3D) .…”