Increased prefrontal cortex interleukin-2 protein levels and shift in the peripheral T cell population in progressive...

Accumulating evidence suggests neuroinflammation to be an integrated feature of neurodegeneration. Profiling inflammatory mediators across diseases may reveal common and disease-specific signatures. Here, we focused on progressive supranuclear palsy (PSP), a tauopathy presenting motor and cognitive dysfunction. We screened for 21 cytokines and growth factors in the dorsomedial prefrontal cortex of 16 PSP and 16 control brains using different quantitative techniques. We found and validated increased interleukin (IL)-2 protein levels in the PSP group expressed locally by neurons and glia cells. We further investigated central players in neuroinflammatory pathways and found increased mRNA expression of glycogen synthase kinase 3 beta (GSK3B). IL-2 and GSK3B proteins are T and natural killer (NK) cell regulators and have previously been associated with other neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and multiple system atrophy. In addition, we identified a shift in peripheral CD4⁺ and CD8⁺ T cell populations toward increased numbers of memory and reduced numbers of naive T cells. We also observed increased numbers of CD56⁺ NK cells, but not of CD56⁺CD57⁺ or CD57⁺ NK cells. Our findings suggest a role for IL-2 in PSP disease processes and point toward active and possibly dysfunctional peripheral immune responses in these patients.