Abstract # 1705 Social regulation of the lymph node transcriptome dynamics in rhesus macaques (Macaca mulatta)

Abstract

Previous work has shown that adverse social conditions may promote a conserved transcriptional response to adversity (CTRA) involving up-regulation of proinflammatory gene expression and down-regulation of Type 1 interferon anti-viral genes in circulating blood cells. This project sought to determine whether social instability in rhesus macaques (N = 10, 5 unstable social conditions, males, mean age = 6.0 years) might exert similar regulatory effects on gene expression within secondary lymphoid tissue (lymph nodes). In parallel with the CTRA pattern observed in peripheral blood mononuclear cells (PBMC), unstable social conditions were linked to lymph node down-regulation of genes involved in Type 1 interferon innate anti-viral responses. Transcript origin analyses implicated monocytes, dendritic cells, and NK cells as mediators of these effects, and promoter-based bioinformatics analyses indicated reduced activity of AP-1, NF-KB, and IRF2 transcription factors in lymph nodes from macaques exposed to unstable social conditions. These results suggest that social influences on immune cell gene regulation are sufficiently pronounced to alter transcriptome profiles in secondary lymphoid tissue, and do so in a regulatory program that resembles that observed in PBMC. Defining the functional impact of these transcriptional alterations represents a primary direction of our future research.