Age-related neuroinflammation and exacerbated immune responses in PINK1 and PARK2 knockout mice with experimental autoimmune encephalomyelitis

Recent studies suggest that the E3 ubiquitin ligase PARKIN and PTEN-induced kinase 1 (PINK1) contribute to age-related immune regulation and neuroinflammation, though the precise mechanisms remain unclear. In this study, we induced active experimental autoimmune encephalomyelitis (EAE) in middle-aged and aged PINK1 ^⁻/⁻ and PARK2 ^⁻/⁻ mice to evaluate their impact on disease progression and immune responses. Flow cytometry, T-cell proliferation assays, and immunohistochemistry were used to analyze peripheral and central nervous system immune responses. Our results show that while both wild-type and knockout mice exhibit reduced disease susceptibility and delayed onset with age, knockout mice develop more severe symptoms and incomplete recovery. This is accompanied by significant alterations in dendritic cells, monocytes, and CD8⁺ T-lymphocytes, as well as increased immune cell infiltration and myeloid activation in the spinal cord. These findings highlight an exaggerated immune response in PINK1 ^- and PARK2 -deficient mice and suggest their involvement in age-related neuroinflammation, potentially through disrupted mitochondrial homeostasis.