Social Regulation of Human and Nonhuman Primate Gene Expression

To identify molecular mechanisms by which early life social conditions might influence adult risk of disease, we analyzed transcriptional remodeling of the basal leukocyte gene expression profile in 4-month-old rhesus macaques (Macaca mulatta) reared under adverse social conditions.  Compared to maternally reared (MR) animals, leukocytes from peer-reared (PR) animals showed enhanced expression of genes involved in inflammation, T lymphocyte activation, and cell proliferation, and suppression of genes involved in Type I Interferon antiviral responses and immunoglobulin production by B lymphocytes.  Promoter-based bioinformatic analyses linked these effects to changes in the activity of transcription factors regulated by the beta-adrenergic / cAMP / PKA signaling pathway, including activation of CREB/ATF, EGR, Ets, GATA, POU/Oct, and C/EBP transcription factors, as well as inhibition of IRF factors.  Provision of an inanimate surrogate mother partially reversed some effects, demonstrating plasticity of transcriptional alterations as a function of social provisions.  These results indicate that social conditions can become embedded into the basal transcriptional stance of the primate immune system within the first 4 months of life, and they identify sympathetic nervous system-linked signal transduction and transcription control pathways as candidate mediators of those effects and potential targets for health-protective intervention.