Distinctive blood CD56bright NK cell subset profile and increased NKG2D expression in CD56bright NK cells in Parkinson’s disease

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Abstract
Mounting data suggest an important role of the immune system in Parkinson’s disease (PD). Previous evidence of increased natural killer (NK) cell populations in PD suggests a potential role of NK cells in the pathogenesis of the disease. Previous studies have analyzed NK populations using aggregation by a variable expression of CD56 and CD16. It remains unknown what differences may exist between NK cell subpopulations when stratified using more nuanced classification. Here we profile NK cell subpopulations and elucidate the expressions of activating NKG2D receptor, inhibitory NKG2A receptor, and homing CX3CR1 receptor on NK cell subpopulations in PD and healthy controls (HC). The cryopreserved PBMC samples were analyzed using a 10-color flow cytometry panel to assess NK cell subpopulations on 36 individuals with sporadic PD and 35 HC participants. Among PD cases, we observed that NKG2D frequency and expression level was higher in CD56bright NK populations in patients with more severe motor symptoms as measured by the UPDRS III. Additionally, NKG2D expression intensity in CD56bright NK populations was associated with disease duration. NK subpopulations revealed a significant difference in CD56brightCD16+/− NK cell subpopulations, with all PD groups showing significantly greater expression of NKG2D on CD56brightCD16bright NK cells compared to HC. Overall, we identified changes in NK profiles in PD that change with disease duration and motor symptom severity. Future studies should assess whether these changes in NK populations account for disease progression.

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