Nocturnal Dim Blue Light Is Associated with Splenic Immune Dysregulation and Altered CORT-GR Signalling in High-Fat-Diet-Fed Mice

Artificial light at night (ALAN) has emerged as a pervasive environmental stressor that disrupts immune homeostasis. This study examined the association between nocturnal dim blue light (dBL) exposure and splenic immune alterations, with particular attention to the corticosterone-glucocorticoid receptor, or CORT-GR, signalling pathway in a high-fat diet-fed mouse model. Male C57BL/6 mice were exposed to dBL (~5 lx) during the dark phase for 12 weeks while maintained on a high-fat diet (HFD). Chronic dBL exposure was associated with splenic atrophy, impaired splenocyte proliferative responses, elevated circulating CORT, and increased splenic GR expression. dBL exposure also coincided with increased NF-κB activation, reduced Nrf2/HO-1 signalling, oxidative stress, and cytokine imbalance in the spleen. Furthermore, in an independent pharmacological cohort, inhibition of CORT synthesis or GR signalling partially attenuated these alterations. Together, these findings suggest that, within an HFD-fed mouse model, dBL exposure is associated with splenic redox-inflammatory imbalance and impaired proliferative responses, a process to which dysregulated CORT-GR signalling appears to contribute.