Brain-Organ Axis: How Stress Regulates Peripheral Immunity Through Neural Signaling

The immune effects of psychological stress differ across cell populations and peripheral organs. Classical endocrine and sympathetic models explain major stress responses, but the contribution of individual brain circuits to specific immune outcomes is less clear. This focused literature review compares neuroendocrine, autonomic and circuit-specific regulation of peripheral immunity through a mouse neural-circuit study and a controlled human viral-challenge study. Glucocorticoid signalling and autonomic relays affect leukocyte trafficking and inflammatory activity. In mice, motor circuits mobilise neutrophils through skeletal-muscle signals while hypothalamic circuits direct monocytes and lymphocytes towards bone marrow; in humans, greater psychological stress before controlled viral exposure is associated with higher susceptibility to respiratory infection. Location and timing affect the outcome. Stress can therefore change both the distribution of immune cells and their functional responses, with the signalling pathway involved, target tissue and timing of the response helping to explain the different consequences of acute and chronic stress and offering measurable targets for studies of neuromodulation and behavioural interventions to improve immune health.