Impaired migratory phenotype of CD4+ T cells in Parkinson's disease

Dejan Mamula; Shervin Khosousi; Yachao He; Vesna Lazarevic; Per Svenningsson

doi:10.1038/s41531-022-00438-0

Impaired migratory phenotype of CD4⁺ T cells in Parkinson's disease

NPJ Parkinsons Dis. 2022 Dec 10;8(1):171. doi: 10.1038/s41531-022-00438-0.

Authors

Dejan Mamula¹, Shervin Khosousi^{2

3}, Yachao He², Vesna Lazarevic², Per Svenningsson^{4

5}

Affiliations

¹ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. dejan_mamula@hotmail.com.
² Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
³ Basic and Clinical Neuroscience, King's College London, London, United Kingdom.
⁴ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. per.svenningsson@ki.se.
⁵ Basic and Clinical Neuroscience, King's College London, London, United Kingdom. per.svenningsson@ki.se.

Abstract

Dysfunctions in the immune system appear implicated in both disease onset and progression of Parkinson's disease (PD). Neurodegeneration observed in the brain of PD patients has been associated with neuroinflammation that is linked to alterations in peripheral adaptive immunity, where CD4⁺ T cells are key players. In the present study, we elucidated the immunological aspect of PD by employing a wide range of cellular assays, immunocytochemistry and flow cytometry to examine CD4⁺ T cells. We particularly investigated the role of CD4⁺ T cell migration in the proper functioning of the adaptive immune system. Our data reveal the altered migration potential of CD4⁺ T cells derived from PD patients, along with impaired mitochondrial positioning within the cell and reduced mitochondrial functionality. In addition, a cross-sectional study of p11 levels in CD4⁺ T cell subsets showed a differentially increased level of p11 in Th1, Th2 and Th17 populations. Taken together, these results demonstrate major impairments in the functionality of peripheral CD4⁺ T cells in PD.