INTRODUCTION: Formyl peptide receptor 2 (FPR2) is a G protein-coupled receptor involved in resolving inflammation and regulating immune and nervous system processes. Its dysfunction is associated with aging-related decline in both systems. One hallmark of immunosenescence is thymic involution—an age-related reduction in thymic size and function, which impairs T cell production. The thymus, essential for the clonal selection and maturation of T lymphocytes, gradually atrophies with age, yet continues to influence immune homeostasis by supporting regulatory T cell (Treg) generation in adulthood.

AIM(S): This study aimed to examine age-related changes in the thymus and brain in FPR2 knockout (FPR2KO) mice compared with wild-type (WT) controls.

METHOD(S): Comparative analyses were conducted in 15- and 18-month-old mice. Relative thymus, brain, and spleen masses were measured. Additionally, FPR2 protein levels were assessed by ELISA in the hippocampus and frontal cortex of WT mice from youth to aging.

RESULTS: Brain mass was significantly reduced in older mice, regardless of genotype. WT mice showed a notable decline in thymus mass with age, confirming thymic involution. In contrast, FPR2KO mice maintained higher thymus mass at both time points, suggesting attenuated involution. FPR2 levels in WT brains varied with age, indicating potential involvement in neural aging.

CONCLUSIONS: These findings suggest that FPR2 may play a key role in regulating thymic aging and maintaining brain homeostasis, linking immune and neural aging through pro-resolving pathways.

FINANCIAL SUPPORT: Grant No. 2021/43/B/NZ4/01133 National Science Centre, Poland, and the Statutory Fund of the Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences.