Oleanane saponin from green tea root extract modulates immune cell function and regulates immunometabolic responses to particulate matter (PM) exposure in PBMCs

Summary: Abstract Body: Exposomal aging is a process influenced by environmental exposures, including but not limited to air pollution. Particulate matter (PM) is an air pollutant associated with increased susceptibility to infectious diseases and is recognized by immune system cells. While the effects of Oleanane saponin-green tea root extract (Senomune) on structural skin cells have been studied, its role in modulating immune cells remains unexplored. In this study, we examined the impact of Senomune (100 µg/mL) by pretreating peripheral blood mononuclear cells (PBMCs) before PM exposure to assess their ability to modulate the immune response. Using a functional Met-Flow assay, we profiled the immune cell landscape, metabolic modifications, and cytokine profile in immune cells pre-treated with Senomune, with or without PM (50 µg/mL) exposure. PBMCs treated with PM alone exhibited a reduction in the number of peripheral T-regulatory (CD4+CD25+) cells (pTregs) and B-cells (CD19+). However, pretreatment with Senomune increased the numbers of pTregs (p<0.0001) and B-cells (p<0.001) in PM-exposed PBMCs. Similarly, PBMCs treated with PM alone showed increased levels of M2 Macrophages (CD11b+CD163+) (p<0.01), which were reduced by treatment with Senomune (p<0.001). Notably, Senomune pretreatment decreased glycolysis (p<0.001), increased OXPHOS (p<0.001), and boosted fatty acid synthesis (p<0.01) in live CD45+ cell populations compared to untreated PBMCs. Furthermore, pretreatment with Senomune also lowered the expression of pro-inflammatory cytokines such as TNF (p<0.001) and IFN-γ (p<0.01) in PM-exposed PBMCs. In summary, pretreatment with Senomune can modulate immune cells and their functions in response to PM exposure and regulate the immunometabolic profile of these immune cells, showing the potential to impact immunosenescence/inflamm-aging. Martin Alphonse¹, Emily Cahill¹, Dustin Dikeman¹, Hye-Won Na², Kyung-Hwan Hwang², Hyoung-June Kim², Sewon Kang¹ 1. Dermatology, Johns Hopkins Medicine, Baltimore, MD, United States. 2. Amorepacific Corporation, Yongsan-gu, Seoul, Korea (the Republic of). Adaptive and Auto-Immunity