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

未经治疗的帕金森病中的调节性损伤并不局限于 Tregs:其他调节性细胞群也参与其中

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作者:Diana D Álvarez-Luquín, Asiel Arce-Sillas, Jaquelín Leyva-Hernández, Edgar Sevilla-Reyes, Marie Catherine Boll, Esteban Montes-Moratilla, Viridiana Vivas-Almazán, Citzielli Pérez-Correa, Ulises Rodríguez-Ortiz, Raquel Espinoza-Cárdenas, Gladis Fragoso, Edda Sciutto, Laura Adalid-Peralta

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.

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.

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-1β, IL-10, TGF-β, 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.

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