Time-resolved RNA signatures of CD4+ T cells in Parkinson’s disease

Abstract

Parkinson’s disease (PD) emerges as a complex, multifactorial disease. While there is increasing evidence that dysregulated T cells play a central role in PD pathogenesis, elucidation of the pathomechanical changes in related signaling is still in its beginnings. We employed time-resolved RNA expression upon the activation of peripheral CD4+ T cells to track and functionally relate changes on cellular signaling in representative cases of patients at different stages of PD. While only few miRNAs showed time-course related expression changes in PD, we identified groups of genes with significantly altered expression for each different time window. Towards a further understanding of the functional consequences, we highlighted pathways with decreased or increased activity in PD, including the most prominent altered IL-17 pathway. Flow cytometric analyses showed not only an increased prevalence of Th17 cells but also a specific subtype of IL-17 producing γδ-T cells, indicating a previously unknown role in PD pathogenesis.

Citation

[22+DHK] Diener, C., Hart, M., Kehl, T., Becker-Dorison, A., Tänzer, T., Schub, D., Krammes, L., Sester, M., Keller, A., Unger, M., Walch-Rückheim, B., Lenhof, H.-P., Meese, E. Time-resolved RNA signatures of CD4+ T cells in Parkinson’s disease. Nature Cell Death Discovery, 2023. DOI: 10.1038/s41420-023-01333-0.
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