INVESTIGATING NEUROIMMUNE SIGNALLING IN DISEASE, STRESS, AND AGEING

Stress activates the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS), driving glucocorticoid and catecholamine release modulating splenic immune function. Although acute activation is adaptive, chronic or dysregulated signalling may promote inflammation and immune dysfunction. How different physiological stressors remodel splenic neuroimmune signalling, and whether these responses differ by sex, remains poorly defined. We investigated whether ageing, stroke, and caloric restriction (CR) induce patterns of splenic neuroimmune remodelling in murine models. Splenic neurotransmitter receptor expression was quantified by qPCR in spleen tissue and isolated lymphocyte populations, while glucocorticoid and catecholamine concentrations were measured in tissue by ELISA. Whole spleen β2-adrenergic receptor (β2-AR) and glucocorticoid receptor expression remained unchanged across conditions, suggesting that tissue-level analysis may mask changes within immune cell subsets. Consistent with this, β2-AR expression was reduced in CD4⁺ T cells acutely following stroke, indicating stressor-specific changes in adrenergic sensitivity in populations of cells. Glucocorticoid concentrations were significantly elevated after stroke and CR, but not ageing, demonstrating divergent endocrine adaptations. Adrenaline levels were unchanged across groups, whereas noradrenaline showed stressor- and sex-dependent regulation: increased following stroke and CR, but reduced with ageing in females only. These findings demonstrate that physiological stressors do not display a uniform splenic stress response, but instead drive selective neuroimmune remodelling. Stroke was associated with an enhanced sympathetic-endocrine profile, CR with a potentially adaptive regulated response, and ageing with impaired noradrenergic signalling, particularly in females. Ongoing immunohistochemical analyses will determine whether these molecular changes are accompanied by alterations in splenic neural and immune cell architecture.