Time-resolved RNA signatures of CD4+ T cells in Parkinson’s disease
Caroline Diener, Martin Hart, Tim Kehl, Anouck Becker-Dorison, Tanja Tänzer, David Schub, Lena Krammes, Martina Sester, Andreas Keller, Marcus M. Unger, Barbara Walch‐Rückheim, Hans‐Peter Lenhof, Eckart Meese
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.