Abstract P190: Social Isolation Associates With The Expression Of NKp46 On Natural Killer Cells Through A Relationship Partially Mediated By RANTES In African-American Women

Abstract

Chronic exposure to psychosocial and environmental stressors (PSES) has been shown to increase risk for diabetes, obesity, and cardiovascular disease and alter immune cell distribution and function. In Natural Killer (NK) cells, the impact of PSES has been demonstrated by a loss of NK cell numbers or function and a shift in NK cell subpopulations. NKp46 is an activating receptor on NK cells crucial for NK cell function. In this study, we aimed to determine if PSES is associated with NKp46 expression. We recruited 27 African-American women (age 59.85±1.91; BMI 34.06±1.67), characterized NKp46 expression from blood samples using flow cytometry, and determined serum cytokine levels using Luminex. Furthermore, study participants answered questionnaires to determine various psychosocial measures, socioeconomic status (SES), and home address for neighborhood deprivation (NDI). First, we determined that social isolation significantly associated with NKp46 expression (β=-0.51, p=0.02), while NDI and SES did not. Second, we identified biomarkers associated with social isolation. Social isolation significantly associated with the cytokine RANTES (β=0.64, p=0.01) after adjustment for cardiovascular risk and BMI. Third, we determined that RANTES also associated with NKp46 expression after adjustment (β=-0.54, p=0.01). We performed a mediation analysis using structural equation modeling to determine if RANTES could be a potential biological mediator between social isolation and NKp46 expression levels; this revealed that RANTES mediates 51.07% of the association (Figure). Thus, our study highlights the importance of further understanding the impact of PSES on immune cells and inflammation. Work to unravel the biology of adversity is crucial to address health disparities. In the future, larger studies should be conducted to identify underlying signaling molecules and pathways altering NK cells during chronic PSES that accelerate disease development and progression and ultimately, serve as targets for intervention.