Early-to-mid stage idiopathic Parkinson’s disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females

Christophe M. Capelle, Séverine Ciré, Fanny Hedin, Maxime Hansen, Lukas Pavelka, Kamil Grzyb, Dimitrios Kyriakis, Oliver Hunewald, Maria Konstantinou, Dominique Revets, Vera Tslaf, Tainá M. Marques, Clarissa P.C. Gomes, Alexandre Baron, Olivia Domingues, Mario Gomez, Ni Zeng, Fay Betsou, Patrick May, Alexander SkupinAntonio Cosma, Rudi Balling, Rejko Krüger, Markus Ollert*, Feng Q. Hefeng*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Neuroinflammation in the brain contributes to the pathogenesis of Parkinson’s disease (PD), but the potential dysregulation of peripheral immunity has not been systematically investigated for idiopathic PD (iPD). Here we showed an elevated peripheral cytotoxic immune milieu, with more terminally-differentiated effector memory (TEMRA) CD8 T, CD8+ NKT cells and circulating cytotoxic molecules in fresh blood of patients with early-to-mid iPD, especially females, after analyzing > 700 innate and adaptive immune features. This profile, also reflected by fewer CD8+FOXP3+ T cells, was confirmed in another subcohort. Co-expression between cytotoxic molecules was selectively enhanced in CD8 TEMRA and effector memory (TEM) cells. Single-cell RNA-sequencing analysis demonstrated the accelerated differentiation within CD8 compartments, enhanced cytotoxic pathways in CD8 TEMRA and TEM cells, while CD8 central memory (TCM) and naïve cells were already more-active and transcriptionally-reprogrammed. Our work provides a comprehensive map of dysregulated peripheral immunity in iPD, proposing candidates for early diagnosis and treatments.

Original languageEnglish
Article number7461
Number of pages21
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - 20 Nov 2023

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