Social Status is Associated with Impaired Anti-Inflammatory Response in Free-Ranging Male Rhesus Macaques

Abstract Exposure to social adversity can influence the onset and progression of disease. One possible mechanism through which may impact health outcomes is by altering immune homeostasis. Recently, evidence has connected changes in gene regulation response both humans nonhuman primates. We investigated how (quantified as low status) affected Th2 free-ranging male rhesus macaques (n=128). stimulated peripheral blood mononuclear cells (PBMCs) vitro with Dexamethasone (Dex), an anti-inflammatory synthetic glucocorticoid (GC), measured status influenced regulatory Dex stimulation using mRNA-seq. detected 2,923 differentially expressed genes (FDR<0.1) PBMCs. After stimulation, responsive genes, such FKBP5 TSCD22, were induced inflammatory CSF1 TNF, repressed. Low animals had significantly higher mean expression (p=1.2×10−20) compared high animals. Many these CD38 NKAP, are known be repressed Dex. also a (p=1.9×10−4) related GC resistance-associated c-Myc/MAPK pathway. For instance, (FDR<0.2) signature this pathway including AKT3, MAPK1 PIK3CD. Our study suggests that negatively status, having blunted presenting signatures resistance. R01-AG060931 R00-AG051764 P40-OD012217