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

Rekha Dhanwani, João Rodrigues Lima-Junior, Ashu Sethi, John Pham, Gregory Williams, April Frazier, Yaqian Xu, Amy W. Amara, David G. Standaert, Jennifer G. Goldman, Irene Litvan, Roy N. Alcalay, Bjoern Peters, David Sulzer, View ORCID ProfileCecilia S. Lindestam Arlehamn, Alessandro Sette
doi: https://doi.org/10.1101/2021.05.28.446215
Rekha Dhanwani
1Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
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João Rodrigues Lima-Junior
1Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
8Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
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Ashu Sethi
1Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
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John Pham
1Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
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Gregory Williams
1Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
8Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
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April Frazier
1Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
8Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
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Yaqian Xu
2Department of Neurology, Columbia University, Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA
8Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
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Amy W. Amara
3Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA
8Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
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David G. Standaert
3Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA
8Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
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Jennifer G. Goldman
4Shirley Ryan AbilityLab, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
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Irene Litvan
5Department of Neuroscience, University of California San Diego, La Jolla, CA, 92093, USA
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Roy N. Alcalay
9Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA
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Bjoern Peters
1Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
6Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
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David Sulzer
2Department of Neurology, Columbia University, Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA
7Departments of Psychiatry and Pharmacology, Columbia University; New York State Psychiatric Institute, New York, NY 10032, USA
8Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
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Cecilia S. Lindestam Arlehamn
1Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
8Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
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  • ORCID record for Cecilia S. Lindestam Arlehamn
  • For correspondence: alex@lji.org cecilia@lji.org
Alessandro Sette
1Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
6Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
8Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
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  • For correspondence: alex@lji.org cecilia@lji.org
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Summary

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 Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 29, 2021.
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Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures
Rekha Dhanwani, João Rodrigues Lima-Junior, Ashu Sethi, John Pham, Gregory Williams, April Frazier, Yaqian Xu, Amy W. Amara, David G. Standaert, Jennifer G. Goldman, Irene Litvan, Roy N. Alcalay, Bjoern Peters, David Sulzer, Cecilia S. Lindestam Arlehamn, Alessandro Sette
bioRxiv 2021.05.28.446215; doi: https://doi.org/10.1101/2021.05.28.446215
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Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures
Rekha Dhanwani, João Rodrigues Lima-Junior, Ashu Sethi, John Pham, Gregory Williams, April Frazier, Yaqian Xu, Amy W. Amara, David G. Standaert, Jennifer G. Goldman, Irene Litvan, Roy N. Alcalay, Bjoern Peters, David Sulzer, Cecilia S. Lindestam Arlehamn, Alessandro Sette
bioRxiv 2021.05.28.446215; doi: https://doi.org/10.1101/2021.05.28.446215

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