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

Area of Science:

• Immunology
• Endocrinology
• Genomics

Background:

• Environmental stress is linked to numerous diseases, including cardiovascular, mental, and autoimmune disorders, primarily through immune system dysregulation.
• Stress hormones like cortisol and norepinephrine, secreted via the hypothalamic-pituitary-adrenal and sympathoadrenal axes, significantly influence immune function, but their precise cellular mechanisms are not fully understood.

Purpose of the Study:

• To investigate the transcriptomic responses of primary immune cells to physiological levels of cortisol and norepinephrine.
• To elucidate cell-type-specific effects of stress hormones on immune function at a single-cell resolution.

Main Methods:

• Utilized an ex vivo model with primary peripheral blood mononuclear cells and neutrophils.
• Applied single-cell RNA sequencing to analyze transcriptomic changes induced by cortisol and norepinephrine exposure.
• Validated stress-related gene signatures in independent human cohorts.

Main Results:

• Identified novel transcriptomic alterations dependent on stress hormones and specific to immune cell types.
• Discovered uniquely regulated genes and inflammation-related signatures in innate immune cells (monocytes/macrophages, neutrophils) and other immune cell populations.
• Demonstrated that single-cell-derived signatures can differentiate individuals with stress-related diseases.

Conclusions:

• Stress hormones induce distinct, cell-type-specific transcriptomic changes in immune cells.
• These stress-induced immune cell signatures are relevant biomarkers for stress-related diseases.
• Provides crucial cell-type-level insights into the immunomodulatory effects of stress hormones in humans.