T cell responses towards PINK1 and α-synuclein are elevated in prodromal Parkinson’s disease
Abstract A role of the immune system in Parkinson’s disease (PD) progression has long been suspected due to the increased frequency of activated glial cells and infiltrating T cells in the substantia nigra. It was previously reported that PD donors have increased T cell responses towards PINK1 and α...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-025-01001-3 |
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| author | Emil Johansson Antoine Freuchet Gregory P. Williams Tanner Michealis April Frazier Irene Litvan Jennifer G. Goldman Roy N. Alcalay David G. Standaert Amy W. Amara Natividad Stover Edward A. Fon Ronald B. Postuma John Sidney David Sulzer Cecilia S. Lindestam Arlehamn Alessandro Sette |
| author_facet | Emil Johansson Antoine Freuchet Gregory P. Williams Tanner Michealis April Frazier Irene Litvan Jennifer G. Goldman Roy N. Alcalay David G. Standaert Amy W. Amara Natividad Stover Edward A. Fon Ronald B. Postuma John Sidney David Sulzer Cecilia S. Lindestam Arlehamn Alessandro Sette |
| author_sort | Emil Johansson |
| collection | DOAJ |
| description | Abstract A role of the immune system in Parkinson’s disease (PD) progression has long been suspected due to the increased frequency of activated glial cells and infiltrating T cells in the substantia nigra. It was previously reported that PD donors have increased T cell responses towards PINK1 and α-synuclein (α-syn), two Lewy body-associated proteins. Further, T cell reactivity towards α-syn was highest closer to disease onset, highlighting that autoreactive T cells might play a role in PD pathogenesis. However, whether T cell autoreactivity is present during prodromal PD is unknown. Here, we investigated T cell responses towards PINK1 and α-syn in donors at high risk of developing PD (i.e. prodromal PD: genetic risk, hyposmia, and or REM sleep behavior disorder), in comparison to PD and healthy control donors. T cell reactivity to these two autoantigens was detected in prodromal PD at levels comparable to those detected in individuals with clinically diagnosed PD. Aligned with the increased incidence of PD in males, we found that males with PD, but not females, had elevated T cell reactivity compared to healthy controls. However, among prodromal PD donors, males and females had elevated T cell responses. These differing trends in reactivity highlights the need for further studies of the impact of biological sex on neuroinflammation and PD progression. |
| format | Article |
| id | doaj-art-e18c78ec4acd439f90c51aabd96d4c9a |
| institution | DOAJ |
| issn | 2373-8057 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-e18c78ec4acd439f90c51aabd96d4c9a2025-08-20T03:22:01ZengNature Portfolionpj Parkinson's Disease2373-80572025-05-011111610.1038/s41531-025-01001-3T cell responses towards PINK1 and α-synuclein are elevated in prodromal Parkinson’s diseaseEmil Johansson0Antoine Freuchet1Gregory P. Williams2Tanner Michealis3April Frazier4Irene Litvan5Jennifer G. Goldman6Roy N. Alcalay7David G. Standaert8Amy W. Amara9Natividad Stover10Edward A. Fon11Ronald B. Postuma12John Sidney13David Sulzer14Cecilia S. Lindestam Arlehamn15Alessandro Sette16Center for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyDepartment of Neuroscience, University of California San DiegoJPG Enterprises LLC (prior: Shirley Ryan Ability Lab and Northwestern University Feinberg School of Medicine)Department of Neurology, Columbia University Irving Medical CenterDepartment of Neurology, University of Alabama at BirminghamDepartment of Neurology, University of Colorado, Anschutz Medical CampusDepartment of Neurology, University of Alabama at BirminghamDepartment of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill UniversityThe Neuro (Montreal Neurological Institute-Hospital), McGill UniversityCenter for Vaccine Innovation, La Jolla Institute for ImmunologyAligning Science Across Parkinson’s (ASAP) Collaborative Research NetworkCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyAbstract A role of the immune system in Parkinson’s disease (PD) progression has long been suspected due to the increased frequency of activated glial cells and infiltrating T cells in the substantia nigra. It was previously reported that PD donors have increased T cell responses towards PINK1 and α-synuclein (α-syn), two Lewy body-associated proteins. Further, T cell reactivity towards α-syn was highest closer to disease onset, highlighting that autoreactive T cells might play a role in PD pathogenesis. However, whether T cell autoreactivity is present during prodromal PD is unknown. Here, we investigated T cell responses towards PINK1 and α-syn in donors at high risk of developing PD (i.e. prodromal PD: genetic risk, hyposmia, and or REM sleep behavior disorder), in comparison to PD and healthy control donors. T cell reactivity to these two autoantigens was detected in prodromal PD at levels comparable to those detected in individuals with clinically diagnosed PD. Aligned with the increased incidence of PD in males, we found that males with PD, but not females, had elevated T cell reactivity compared to healthy controls. However, among prodromal PD donors, males and females had elevated T cell responses. These differing trends in reactivity highlights the need for further studies of the impact of biological sex on neuroinflammation and PD progression.https://doi.org/10.1038/s41531-025-01001-3 |
| spellingShingle | Emil Johansson Antoine Freuchet Gregory P. Williams Tanner Michealis April Frazier Irene Litvan Jennifer G. Goldman Roy N. Alcalay David G. Standaert Amy W. Amara Natividad Stover Edward A. Fon Ronald B. Postuma John Sidney David Sulzer Cecilia S. Lindestam Arlehamn Alessandro Sette T cell responses towards PINK1 and α-synuclein are elevated in prodromal Parkinson’s disease npj Parkinson's Disease |
| title | T cell responses towards PINK1 and α-synuclein are elevated in prodromal Parkinson’s disease |
| title_full | T cell responses towards PINK1 and α-synuclein are elevated in prodromal Parkinson’s disease |
| title_fullStr | T cell responses towards PINK1 and α-synuclein are elevated in prodromal Parkinson’s disease |
| title_full_unstemmed | T cell responses towards PINK1 and α-synuclein are elevated in prodromal Parkinson’s disease |
| title_short | T cell responses towards PINK1 and α-synuclein are elevated in prodromal Parkinson’s disease |
| title_sort | t cell responses towards pink1 and α synuclein are elevated in prodromal parkinson s disease |
| url | https://doi.org/10.1038/s41531-025-01001-3 |
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