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

Author

Listed:
  • Christophe M. Capelle

    (Luxembourg Institute of Health (LIH)
    University of Luxembourg
    ETH Zurich)

  • Séverine Ciré

    (Luxembourg Institute of Health (LIH)
    Eligo Bioscience)

  • Fanny Hedin

    (Luxembourg Institute of Health (LIH))

  • Maxime Hansen

    (University of Luxembourg
    Centre Hospitalier de Luxembourg (CHL))

  • Lukas Pavelka

    (University of Luxembourg
    Centre Hospitalier de Luxembourg (CHL)
    Luxembourg Institute of Health (LIH))

  • Kamil Grzyb

    (University of Luxembourg)

  • Dimitrios Kyriakis

    (University of Luxembourg
    Icahn School of Medicine at Mount Sinai)

  • Oliver Hunewald

    (Luxembourg Institute of Health (LIH))

  • Maria Konstantinou

    (Luxembourg Institute of Health (LIH))

  • Dominique Revets

    (Luxembourg Institute of Health (LIH))

  • Vera Tslaf

    (Luxembourg Institute of Health (LIH)
    University of Luxembourg
    Luxembourg Institute of Health (LIH))

  • Tainá M. Marques

    (Luxembourg Institute of Health (LIH))

  • Clarissa P. C. Gomes

    (University of Luxembourg)

  • Alexandre Baron

    (Luxembourg Institute of Health (LIH))

  • Olivia Domingues

    (Luxembourg Institute of Health (LIH))

  • Mario Gomez

    (Luxembourg Institute of Health (LIH))

  • Ni Zeng

    (Luxembourg Institute of Health (LIH)
    University of Luxembourg)

  • Fay Betsou

    (Integrated Biobank of Luxembourg (IBBL), Luxembourg Institute of Health (LIH)
    Université Paris Cité)

  • Patrick May

    (University of Luxembourg)

  • Alexander Skupin

    (University of Luxembourg
    University of Luxembourg
    University California San Diego School of Medicine)

  • Antonio Cosma

    (Luxembourg Institute of Health (LIH))

  • Rudi Balling

    (University of Luxembourg
    University of Bonn)

  • Rejko Krüger

    (University of Luxembourg
    Centre Hospitalier de Luxembourg (CHL)
    Luxembourg Institute of Health (LIH))

  • Markus Ollert

    (Luxembourg Institute of Health (LIH)
    Odense Research Center for Anaphylaxis (ORCA), University of Southern Denmark)

  • Feng Q. Hefeng

    (Luxembourg Institute of Health (LIH)
    Data Integration and Analysis Unit, Luxembourg Institute of Health (LIH))

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.

Suggested Citation

  • 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., 2023. "Early-to-mid stage idiopathic Parkinson’s disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43053-0
    DOI: 10.1038/s41467-023-43053-0
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    References listed on IDEAS

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