Brain microglia activation and peripheral adaptive immunity in Parkinson's disease: a multimodal PET study.

BACKGROUND: Abnormal activation of immune system is an important pathogenesis of Parkinson's disease, but the relationship between peripheral inflammation, central microglia activation and dopaminergic degeneration remains unclear. OBJECTIVES: To evaluate the brain regional microglia activation and its relationship with clinical severity, dopaminergic presynaptic function, and peripheral inflammatory biomarkers related to adaptive immunity. METHODS: In this case-control study, we recruited 23 healthy participants and 24 participants with early-stage Parkinson's disease. 18F-PBR06 PET/MR for microglia activation, 18F-FP-DTBZ for dopaminergic denervation, total account of T cells and subpopulations of T helper (Th1/Th2/Th17) cells, and the levels of serum inflammatory cytokines were assessed. Sanger sequencing was used to exclude the mix-affinity binders of 18F-PBR06-PET. RESULTS: Compared to healthy controls, patients with Parkinson's disease had an increased 18F-PBR06-PET standardized uptake value ratio (SUVR) in the putamen, particularly in the ipsilateral side of the motor onset. 18F-PBR06-PET SUVR was positively associated with 18F-FP-DTBZ-PET SUVR in the brainstem and not associated with disease severity measured by Hoehn and Yahr stage, MDS-UPDRS III scores. Patients with Parkinson's disease had elevated frequencies of Th1 cells and serum levels of IL10 and IL17A as compared to healthy controls. No significant association between peripheral inflammation markers and microglia activation in the brain of PD was observed. CONCLUSION: Parkinson's disease is associated with early putaminal microglial activation and peripheral phenotypic Th1 bias. Peripheral adaptive immunity might be involved in microglia activation in the process of neurodegeneration in PD indirectly, which may be a potential biomarker for the early detection and the target for immunomodulating therapy.

Aging, rather than Parkinson's disease, affects the responsiveness of PBMCs to the immunosuppression of bone marrow mesenchymal stem cells.

Whether aging or Parkinson's disease (PD) affects the responses of peripheral blood mononuclear cells (PBMCs) to immunosuppression by bone marrow­derived mesenchymal stem cell (BM­MSCs) and which cytokines are more effective in inducing BM­MSCs to be immunosuppressive remains to be elucidated. PBMCs were isolated from healthy young (age 26­35), healthy middle­aged (age 56­60) and middle­aged PD­affected individuals. All the recruits were male. The mitogen­stimulated PBMCs and proinflammatory cytokine­pretreated BM­MSCs were co­cultured. The PBMC proliferation was measured using Cell Counting Kit­8, while the cytokine secretion was assayed by cytometric bead array technology. The immunosuppressive ability of BM­MSCs was confirmed in young healthy, middle­aged healthy and middle­aged PD­affected individuals. Among the three groups, the PBMC proliferation and cytokine secretion of the young healthy group were suppressed more significantly compared with those of the middle­aged healthy and middle­aged PD­affected group. No significant differences were identified in the PBMC proliferation and cytokine secretion between the patients with PD and the middle­aged healthy subjects. Interferon (IFN)­Î³ synergized with tumor necrosis factor (TNF)­α, interleukin (IL)­1α or IL­1ß was more effective than either one alone, and the combinations of IFN­Î³ + IL­1α and IFN­Î³ + IL­1ß were more effective than IFN­Î³ + TNF­α in inducing BM­MSCs to inhibit PBMC proliferation. The results of the present study suggested that aging, rather than PD, affects the response of PBMCs toward the suppression of BM­MSC, at least in middle­aged males. Patients with PD aged 56­60 remain eligible for anti­inflammatory BM­MSC­based therapy. Treatment of BM­MSCs with IFN­Î³ + IL­1α or IFN­Î³ + IL­1ß prior to transplantation may result in improved immunosuppressive effects.