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Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures

ABSTRACT: Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures

PROVIDER: PRJNA730004 | ENA |

REPOSITORIES: ENA

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Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures

Project description:Parkinson’s disease (PD) is a multi-stage neurodegenerative disorder with largely unknown etiology. To further characterize the role of T cells in PD associated autoimmunity, we performed RNA sequencing on PBMC and peripheral CD4 and CD8 memory T cell subsets derived from PD patients and age-matched healthy controls. Considering T cell reactivity to -syn, the study revealed a broad differential gene expression profile in memory T cell subsets and a specific PD associated gene signature. This study found a significant enrichment of transcriptomic signatures previously associated with PD, such as oxidative stress and phosphorylation, autophagy of mitochondria, cholesterol metabolism, and inflammation. We also identified novel genes associated with PD, including xx. Altogether, the findings in this study suggest that the study of circulating T cells from PD subjects with an ongoing -syn-specific T cell response may provide new insights to understand the complexity of the disease and suggest potential intervention targets.

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Transcriptional analysis of peripheral memory T cells reveals Parkinson's disease-specific gene signatures.

Project description: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 an 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 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.

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