Abstract
Parkinson’s disease (PD) is characterised by α-synuclein aggregation, dopaminergic neuron loss and chronic neuroinflammation. Disruption of the blood-brain barrier enables immune cell infiltration, including dendritic cells (DCs) and CD4+ T-cells, contributing to disease progression. To explore peripheral immune mechanisms in PD, we isolated DCs and CD4+ T-cells from the blood of 17 PD patients and 10 controls using magnetic separation, followed by flow cytometry and single-cell RNA sequencing. Cell-type annotation identified CD4+ T-cell and DC subtypes, including rare DC3 cells. PD patients showed reduced circulating DCs, with no change in CD4+ T-cell levels. Differential gene expression and pathway analysis suggest CD4+ effector memory T-cells (TEMs) and cDC2s as important mediators of immune responses in PD, enriched for immune-related pathways including T-cell activation and antigen presentation. Our findings implicate specific immune subsets in PD-associated neuroinflammation, suggesting cDC2s and CD4+ TEMs as potential targets for immunomodulatory strategies.
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Data availability
The single-cell RNA sequencing data obtained during this study will be made publicly available in the GitHub repository [https://github.com/PKatarina/PD_SingleCell] at the publication date of this article. All other data supporting this study are available from the corresponding authors upon reasonable request.
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Acknowledgements
We thank nurse Andrea Klokočki from University Hospital Centre Zagreb for her valuable assistance in collecting blood samples and gratefully acknowledge all study participants for their generous contribution to this research. This study was conducted as a part of the ‘Molecular mechanisms of immune response and inflammasome activation in Parkinson's disease’ project (IP-2020-02-8475) funded by the Croatian Science Foundation. Sarah Meglaj Bakrač is funded by the Croatian Science Foundation’s Young Researchers’ Career Development Project, DOK-2021-02-5343. Katarina Mandić is funded by the Croatian Science Foundation project UIP-2020-02-1623. The funder played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript.
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S.M.B. and A.B. performed single-cell sequencing experiments, data analysis and visualisation. K.M. conducted bioinformatics analysis, coding and visualisation of single-cell sequencing data. A.Ba. contributed to bioinformatics analysis, conceptualisation and supervision. F.B. selected participants and collected the samples. Z.M.S. and L.C.K. carried out PBMC isolation, magnetic separation, flow cytometry and flow cytometry data analysis and visualisation. F.B. acquired funding, supervised the project and validated the results. S.M.B., K.M., A.B. and Z.M.S. drafted the original manuscript. All authors reviewed, edited and approved the final manuscript.
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Meglaj Bakrač, S., Mandić, K., Cvetko Krajinović, L. et al. Single-cell analysis of the peripheral immune landscape in Parkinson’s disease: insights into dendritic cell and CD4+ T-cell transcriptomics. npj Parkinsons Dis. (2026). https://doi.org/10.1038/s41531-026-01283-1
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DOI: https://doi.org/10.1038/s41531-026-01283-1
