Melatonin nuclear receptors mediate monochromatic light-induced T-lymphocyte proliferation of thymus through the AKT/GSK3β/β-catenin pathway in chick

Based on previous research, it's unclear about the signaling pathway involved in the negative regulation of T-lymphocyte proliferation in thymus by monochromatic red light. Newly hatched chicks were randomly assigned divided into white (WL), red (RL), green (GL), and blue (BL) light treatments. Three days later, each light treatment group was further divided into intact, sham operation, and pinealectomy groups. The findings revealed that RL led to an increase in the expression of RORα and RORγ, while p-AKT/p-GSK3β/β-catenin/CyclinD1 expression in the thymus of chicks were decreased. Conversely, GL showed opposite results compared to RL. After pinealectomy, accompanied with the expression of RORα and RORγ increased under four light, p-AKT/ p-GSK3β/ β-catenin/ CyclinD1 expression were decreased. In vitro, exogenous melatonin increased the p-AKT/β-catenin/CyclinD1 expression in the thymic lymphocytes of chick reared under RL. The stimulative effect of melatonin was enhanced by SR3335 (RORα antagonist) or GSK298 (RORγ antagonist), while it was attenuated by SR1078 (RORα/RORγ agonist), LY-294 (PI3K antagonist) and HY-102 (AKT antagonist). These results demonstrate that RORα/RORγ negatively regulate monochromatic red light induced-T-lymphocyte proliferation in the thymus, possibly through the PI3K/AKT/p-GSK3β (Ser9) signaling pathway.