Single-cell transcriptomics provides insights into the stress-immune interplay and informs disease risk

Stress operates through the hypothalamic-pituitary-adrenal and sympathoadrenal axes, leading to peripheral secretion of cortisol and norepinephrine, respectively. While stress hormones can profoundly influence immune function, their mechanistic effects at the cell-type level remain poorly understood.

To address this knowledge gap, we employed an ex vivo model investigating the transcriptomic responses of primary peripheral blood mononuclear cells and neutrophils to physiological stress levels (i.e., levels reached during in vivo stress) of cortisol and norepinephrine at single-cell resolution. We identified novel stress-hormone-dependent and cell-type-specific transcriptomic changes, including uniquely regulated genes and inflammation-related signatures within distinct innate (e.g., CD163+ monocytes/macrophages, neutrophils) and other immune cell types.