Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures
Abstract 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 perip...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-03-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-022-00282-2 |
| _version_ | 1797642683937718272 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Rekha Dhanwani |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-11T14:04:48Z |
| format | Article |
| id | doaj.art-fb806e6ca1ad4d80bc031c69934a1768 |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-11T14:04:48Z |
| publishDate | 2022-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-fb806e6ca1ad4d80bc031c69934a17682023-11-02T03:21:10ZengNature Portfolionpj Parkinson's Disease2373-80572022-03-018111010.1038/s41531-022-00282-2Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signaturesRekha Dhanwani0João Rodrigues Lima-Junior1Ashu Sethi2John Pham3Gregory Williams4April Frazier5Yaqian Xu6Amy W. Amara7David G. Standaert8Jennifer G. Goldman9Irene Litvan10Roy N. Alcalay11Bjoern Peters12David Sulzer13Cecilia S. Lindestam Arlehamn14Alessandro Sette15Division of Vaccine Discovery, La Jolla Institute for ImmunologyDivision of Vaccine Discovery, La Jolla Institute for ImmunologyDivision of Vaccine Discovery, La Jolla Institute for ImmunologyDivision of Vaccine Discovery, La Jolla Institute for ImmunologyDivision of Vaccine Discovery, La Jolla Institute for ImmunologyDivision of Vaccine Discovery, La Jolla Institute for ImmunologyAligning Science Across Parkinson’s (ASAP) Collaborative Research NetworkAligning Science Across Parkinson’s (ASAP) Collaborative Research NetworkAligning Science Across Parkinson’s (ASAP) Collaborative Research NetworkShirley Ryan AbilityLab, Northwestern University Feinberg School of MedicineDepartment of Neuroscience, University of California San DiegoDepartment of Neurology, Columbia University Irving Medical CenterDivision of Vaccine Discovery, La Jolla Institute for ImmunologyAligning Science Across Parkinson’s (ASAP) Collaborative Research NetworkDivision of Vaccine Discovery, La Jolla Institute for ImmunologyDivision of Vaccine Discovery, La Jolla Institute for ImmunologyAbstract 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.https://doi.org/10.1038/s41531-022-00282-2 |
| spellingShingle | 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 Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures npj Parkinson's Disease |
| title | Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures |
| title_full | Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures |
| title_fullStr | Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures |
| title_full_unstemmed | Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures |
| title_short | Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures |
| title_sort | transcriptional analysis of peripheral memory t cells reveals parkinson s disease specific gene signatures |
| url | https://doi.org/10.1038/s41531-022-00282-2 |
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