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Cited by 134Parkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsNuclear Receptors and Signaling

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Immune Cell Activation in the Cerebrospinal Fluid of Patients With Parkinson's Disease

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Schröder, Jens B., Pawlowski, Matthias, Meyer zu Hörste, Gerd, Gross, Catharina C., Wiendl, Heinz, Meuth, Sven G., Ruck, Tobias, Warnecke, Tobias·2018·Frontiers in Neurology
DOI 10.3389/fneur.2018.01081PMC PMC6305582
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Abstract

Background: Parkinson’s disease (PD) is a common neurodegenerative disorder. The contribution of the immune system to its pathogenesis remains incompletely understood. Methods: In this study, we performed comprehensive immune cell profiling in the cerebrospinal fluid (CSF) and peripheral blood (PB) of PD patients. Ten PD patients were diagnosed according to brain bank criteria and underwent detailed clinical examination, magnetic resonance imaging, PB and CSF immune cell profiling by multiparameter flow cytometry, and cytokine and chemokine measurements by bead-based arrays. Thirteen healthy elderly volunteers served as control population. Results: The proportions of activated T-lymphocytes and nonclassical monocytes in the CSF were increased in patients with PD compared to the control group. In accordance, we found increased levels of the pro-inflammatory cytokines IL-2, IL-6 and TNFα and of the monocyte chemoattractant protein 1 (MCP-1) in the CSF of the included PD patients. Conclusions: Our data provide novel evidence for a response of the innate and adaptive immune system in the central nervous system of patients with PD.

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Figure 1 Monocytes in the peripheral blood and cerebrospinal fluid. The proportion of monocytes in relation to total leukocytes was determined in the peripheral blood (PB, closed symbols, white background) and cerebrospinal fluid (CSF, open symbols, gray background) from healthy elderly controls (n = 13; blue circles) and PD patients (n = 10; red triangles). While the proportion of total monocytes did not differ between study groups, monocyte subgroup analysis based on expression of the surface marker CD16 demonstrated a highly significant decrease of classical monocytes (CD14+CD16−) and a concomitant highly significant increase of non-classical monocytes (CD14+CD16+). For statistical analysis, the Mann-Whitney test was performed (***p < 0.001).
Figure 1 Monocytes in the peripheral blood and cerebrospinal fluid. The proportion of monocytes in relation to total leukocytes was determined in the peripheral blood (PB, closed symbols, white background) and cerebrospinal fluid (CSF, open symbols, gray background) from healthy elderly controls (n = 13; blue circles) and PD patients (n = 10; red triangles). While the proportion of total monocytes did not differ between study groups, monocyte subgroup analysis based on expression of the surface marker CD16 demonstrated a highly significant decrease of classical monocytes (CD14+CD16−) and a concomitant highly significant increase of non-classical monocytes (CD14+CD16+). For statistical analysis, the Mann-Whitney test was performed (***p < 0.001).CC BY · PubMed Central
Figure 2 Lymphocytes in the peripheral blood and cerebrospinal fluid. The proportion of T lymphocytes in relation to total leukocytes was determined in the peripheral blood (PB, closed symbols, white background) and cerebrospinal fluid (CSF, open symbols, gray background) from healthy elderly controls (n = 13; blue circles) and PD patients (n = 10; red triangles). We found a significant increase of total and activated T lymphocytes in the CSF. CD4 and CD8 expression did not differ between study groups, but specifically CD8+ T lymphocytes displayed a larger fraction of HLA-DR expressing activated cells, both in the PB and CSF. For statistical analysis, the Mann-Whitney test was performed (*p < 0.05, **p < 0.01, ***p < 0.001).
Figure 2 Lymphocytes in the peripheral blood and cerebrospinal fluid. The proportion of T lymphocytes in relation to total leukocytes was determined in the peripheral blood (PB, closed symbols, white background) and cerebrospinal fluid (CSF, open symbols, gray background) from healthy elderly controls (n = 13; blue circles) and PD patients (n = 10; red triangles). We found a significant increase of total and activated T lymphocytes in the CSF. CD4 and CD8 expression did not differ between study groups, but specifically CD8+ T lymphocytes displayed a larger fraction of HLA-DR expressing activated cells, both in the PB and CSF. For statistical analysis, the Mann-Whitney test was performed (*p < 0.05, **p < 0.01, ***p < 0.001).CC BY · PubMed Central
Figure 3 Cytokine and chemokine production in the cerebrospinal fluid. The concentrations of cytokines and chemokines were determined in the cerebrospinal fluid from healthy elderly controls (n = 11; blue circles) and PD patients (n = 7; red triangles) by a bead-based cytokine array. We found a significant increase of the pro-inflammatory cytokines IL-2, IL-6, and TNFα as well as of the pro-migratory chemokine MCP-1 in the CSF of PD patients, whereas anti-inflammatory IL-9 was decreased. For statistical analysis, the Mann-Whitney test was performed (*p < 0.05).
Figure 3 Cytokine and chemokine production in the cerebrospinal fluid. The concentrations of cytokines and chemokines were determined in the cerebrospinal fluid from healthy elderly controls (n = 11; blue circles) and PD patients (n = 7; red triangles) by a bead-based cytokine array. We found a significant increase of the pro-inflammatory cytokines IL-2, IL-6, and TNFα as well as of the pro-migratory chemokine MCP-1 in the CSF of PD patients, whereas anti-inflammatory IL-9 was decreased. For statistical analysis, the Mann-Whitney test was performed (*p < 0.05).CC BY · PubMed Central

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Metadata

Authors
Schröder, J. B., Pawlowski, M., Meyer zu Hörste, G., Gross, C. C., Wiendl, H., Meuth, S. G., Ruck, T., & Warnecke, T.
Affiliations
University Hospital Münster (DE)
Corresponding author
Warnecke, Tobias
ORCID
Venue
Frontiers in Neurology
Publisher
Frontiers Media SA
Published
2018-12-18
Volume
9
Pages
1081-1081
ISSN
1664-2295 (ISSN-L)
DOI
10.3389/fneur.2018.01081
PMC
PMC6305582
OpenAlex
W2903888966
Cited by
134
References
46
Citations by year
2026: 11 · 2025: 17 · 2024: 22 · 2023: 20 · 2022: 25 · 2021: 10 · 2020: 22 · 2019: 7
FWCI
6.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neurology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • URN:NBN Resolver for Germany & Switzerland (German National Library) (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords
Parkinson's disease, cerebrospinal fluid, immune cell activation, T cells, non-classical monocytes, inflammatory cytokines, interleukin-6, TNF-α, interleukin-2, MCP-1, chemokines, innate and adaptive immunity, neuroinflammation

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