TY - JOUR T1 - Distinct inflammatory and transcriptomic profiles in dominant versus subordinate males in mouse social hierarchies JF - bioRxiv DO - 10.1101/2021.09.04.458987 SP - 2021.09.04.458987 AU - Won Lee AU - Tyler M. Milewski AU - Madeleine F. Dwortz AU - Rebecca L. Young AU - Andrew D. Gaudet AU - Laura K. Fonken AU - Frances A. Champagne AU - James P. Curley Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/09/06/2021.09.04.458987.abstract N2 - Social status is a critical factor determining health outcomes in human and nonhuman social species. In social hierarchies with reproductive skew, individuals compete to monopolize resources and increase mating opportunities. This can come at a significant energetic cost leading to trade-offs between different physiological systems. Particularly, changes in energetic investment in the immune system can have significant short and long-term effects on fitness and health. We have previously found that dominant alpha male mice living in social hierarchies have increased metabolic demands related to territorial defense. In this study, we tested the hypothesis that high-ranking male mice favor energetically inexpensive adaptive immunity, while subordinate mice show higher investment in innate immunity. We housed 12 groups of 10 outbred CD-1 male mice in a social housing system. All formed linear social hierarchies and subordinate mice had higher concentrations of plasma corticosterone (CORT) than alpha males. This difference was heightened in highly despotic hierarchies. Using flow cytometry, we found that dominant status was associated with a significant shift in immunophenotypes towards favoring adaptive versus innate immunity. Using Tag-Seq to profile hepatic and splenic transcriptomes of alpha and subordinate males, we identified genes that regulate metabolic and immune defense pathways that are associated with status and/or CORT concentration. In the liver, dominant animals showed an up-regulation of specific genes involved in major urinary production and catabolic processes, whereas subordinate animals showed an up-regulation of genes promoting biosynthetic processes, wound healing, and proinflammatory responses. In spleen, subordinate mice showed up-regulation of genes facilitating oxidative phosphorylation and DNA repair and CORT was negatively associated with genes involved in lymphocyte proliferation and activation. Together, our findings suggest that dominant and subordinate animals adaptively shift energy investment in immune functioning and gene expression to match their contextual energetic demands.Immunity is shaped by stress and energetic pressures associated with social statusDominant and subordinate mice favor adaptive and innate immunity, respectivelyDominants increase expression of genes involved in energy productionWound healing and DNA repair genes are upregulated in subordinatesGenes related to maintaining and signaling social status are upregulated in dominantsCompeting Interest StatementThe authors have declared no competing interest. ER -