Cytokine and chemokine map of peripheral specific immune cell subsets in Parkinson's disease

Peripheral immune cells play a vital role in the development of Parkinson's disease (PD). However, their cytokine and chemokine secretion functions remain unclear. Therefore, we aimed to explore the cytokine and chemokine secretion functions of specific immune cell subtypes in drug-naive patients with PD at different ages of onset. We included 10 early-onset and 10 late-onset patients with PD and age-matched healthy controls (HCs). We used mass cytometry to select specific immune cell subsets and evaluate intracellular cytokine and chemokine expression. Statistical tests included t-tests, analysis of variance, bivariate correlation analysis, and linear regression analysis. Compared with HCs, patients with PD exhibited significantly decreased intracellular pro-inflammatory cytokines and chemokines in selected clusters (e.g., tumor necrosis factor (TNF)-& alpha;, interleukin (IL)-8, IL-1 & beta;, and CC-chemokine ligand (CCL)17). Specific cytokines and cell clusters were associated with clinical symptoms. TNF-& alpha; played an important role in cognitive impairment. Intracellular TNF-& alpha; levels in the naive CD8(+) T-cell cluster C16 (CD57(-) naive CD8(+) T) and natural killer (NK) cell cluster C32 (CD57(-) CD28(-) NK) were negatively correlated with Montreal Cognitive Assessment scores. The C16 cluster affected cognitive function and motor symptoms. Increased TNF-& alpha; and decreased interferon-& gamma; expression in C16 correlated with increased Unified Parkinson's Disease Rating Scale III scores in patients with PD. In summary, we developed a more detailed cytokine and chemokine map of peripheral specific CD8(+) T cell and NK cell subsets, which revealed disrupted secretory function in patients with PD and provided unique clues for further mechanistic exploration.

Automated summary

Peripheral immune cells, specifically CD8(+) T cells and NK cells, in patients with Parkinson's disease (PD) exhibit disrupted secretion of pro-inflammatory cytokines and chemokines, such as TNF-& alpha;, IL-8, IL-1 & beta;, and CCL17. These cytokines and cell clusters are associated with clinical symptoms, including cognitive impairment and motor symptoms. The levels of intracellular TNF-& alpha; in CD8(+) T cells and NK cells are negatively correlated with cognitive assessment scores and positively correlated with the severity of motor symptoms. This study provides important insights into the role of peripheral immune cells in PD pathogenesis.