RT Journal Article
SR Electronic
T1 Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.28.446215
DO 10.1101/2021.05.28.446215
A1 Rekha Dhanwani
A1 João Rodrigues Lima-Junior
A1 Ashu Sethi
A1 John Pham
A1 Gregory Williams
A1 April Frazier
A1 Yaqian Xu
A1 Amy W. Amara
A1 David G. Standaert
A1 Jennifer G. Goldman
A1 Irene Litvan
A1 Roy N. Alcalay
A1 Bjoern Peters
A1 David Sulzer
A1 Cecilia S. Lindestam Arlehamn
A1 Alessandro Sette
YR 2021
UL http://biorxiv.org/content/early/2021/05/29/2021.05.28.446215.abstract
AB Parkinson’s disease (PD) is a multi-stage neurodegenerative disorder with largely unknown etiology. Recent findings have identified PD-associated autoimmune features including roles for T cells. To further characterize the role of T cells in PD, we performed RNA sequencing on PBMC and peripheral CD4 and CD8 memory T cell subsets derived from PD patients and age-matched healthy controls. When the groups were stratified by their T cell responsiveness to alpha-synuclein (α-syn) as a proxy for ongoing inflammatory autoimmune response, the study revealed a broad differential gene expression profile in memory T cell subsets and a specific PD associated gene signature. We identified a significant enrichment of transcriptomic signatures previously associated with PD, including for oxidative stress, phosphorylation, autophagy of mitochondria, cholesterol metabolism and inflammation, and the chemokine signaling proteins CX3CR1, CCR5 and CCR1. In addition, we identified genes in these peripheral cells that have previously been shown to be involved in PD pathogenesis and expressed in neurons, such as LRRK2, LAMP3, and aquaporin. Together, these findings suggest that features of circulating T cells with α-syn-specific responses in PD patients provide insights into the interactive processes that occur during PD pathogenesis and suggest potential intervention targets.Competing Interest StatementThe authors have declared no competing interest.