Increased levels of regulatory T cells and IL-10-producing regulatory B cells are linked to improved clinical outcome in Parkinson's disease: a 1-year observational study.

Whilst the contribution of peripheral and central inflammation to neurodegeneration in Parkinson's disease and the role of the immune response in this disorder are well known, the effects of the anti-inflammatory response on the disease have not been described in depth. This study is aimed to assess the changes in the regulatory/inflammatory immune response in recently diagnosed, untreated PD patients and a year after. Twenty-one PD patients and 19 healthy controls were included and followed-up for 1 year. The levels of immunoregulatory cells (CD4+ Tregs, Bregs, and CD8+ Tregs); classical, nonclassical, and intermediate monocytes, and proinflammatory cells (Th1, Th2, and Th17) were measured by flow cytometry. Cytokine levels were determined by ELISA. Clinical follow-up was based on the Hoehn & Yahr and UDPRS scales. Our results indicate that the regulatory response in PD patients on follow-up was characterized by increased levels of active Tregs, functional Tregs, TR1, IL-10-producing functional Bregs, and IL-10-producing classical monocytes, along with decreased counts of Bregs and plasma cells. With respect to the proinflammatory immune response, peripheral levels of Th1 IFN-γ+ cells were decreased in treated PD patients, whilst the levels of CD4+ TBET+ cells, HLA-DR+ intermediate monocytes, IL-6, and IL-4 were increased after a 1-year follow-up. Our main finding was an increased regulatory T cell response after a 1-year follow-up and its link with clinical improvement in PD patients. In conclusion, after a 1-year follow-up, PD patients exhibited increased levels of regulatory populations, which correlated with clinical improvement. However, a persistent inflammatory environment and active immune response were observed.

Regulatory impairment in untreated Parkinson's disease is not restricted to Tregs: other regulatory populations are also involved.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Various studies have suggested that the immune response plays a key role in this pathology. While a predominantly pro-inflammatory peripheral immune response has been reported in treated and untreated PD patients, the study of the role of the regulatory immune response has been restricted to regulatory T cells. Other immune suppressive populations have been described recently, but their role in PD is still unknown. This study was designed to analyze the pro and anti-inflammatory immune response in untreated PD patients, with emphasis on the regulatory response. METHODS: Thirty-two PD untreated patients and 20 healthy individuals were included in this study. Peripheral regulatory cells (CD4+Tregs, Bregs, CD8+Tregs, and tolerogenic dendritic cells), pro-inflammatory cells (Th1, Th2, and Th17 cells; active dendritic cells), and classical, intermediate, and non-classical monocytes were characterized by flow cytometry. Plasmatic levels of TNF-α, IFN-γ, IL-6, GM-CSF, IL-12p70, IL-4, IL-13, IL-17α, IL-1ß, IL-10, TGF-ß, and IL-35 were determined by ELISA. RESULTS: Decreased levels of suppressor Tregs, active Tregs, Tr1 cells, IL-10-producer CD8regs, and tolerogenic PD-L1+ dendritic cells were observed. With respect to the pro-inflammatory response, a decrease in IL-17-α and an increase in IL-13 levels were observed. CONCLUSION: A decrease in the levels of regulatory cell subpopulations in untreated PD patients is reported for the first time in this work. These results suggest that PD patients may exhibit a deficient suppression of the pro-inflammatory response, which could contribute to the pathophysiology of the disease.