Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Nov 11;16(1):212.
doi: 10.1186/s12974-019-1606-1.

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

Diana D Álvarez-Luquín  1 , Asiel Arce-Sillas  1 , Jaquelín Leyva-Hernández  1 , Edgar Sevilla-Reyes  2 , Marie Catherine Boll  3 , Esteban Montes-Moratilla  1 , Viridiana Vivas-Almazán  1 , Citzielli Pérez-Correa  1 , Ulises Rodríguez-Ortiz  3 , Raquel Espinoza-Cárdenas  1 , Gladis Fragoso  4 , Edda Sciutto  4 , Laura Adalid-Peralta  5   6
Affiliations

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

Diana D Álvarez-Luquín et al. J Neuroinflammation. .

Abstract

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-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.

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.

Keywords: Bregs; CD8regs; Parkinson’s disease; Peripheral immune response; Tregs; Untreated patients.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Decreased levels of active Tregs, suppressor Tregs, and Tr1 cells in PD patients. Differences between controls (Ctr) and PD patients (PD) are shown. The percentage corresponding to each cell phenotype is shown on the y-axis. *P <  0.05 is considered as significant, **P <  0.005 is considered as significant
Fig. 2
Fig. 2
Increased plasmatic levels of IL-13 and decreased levels of IL-17A in PD patients. The plasmatic levels of regulatory (IL-10, IL-35, and TGF-β) and pro-inflammatory cytokines (IL-1β, IL-6, IL-12p70, and GM-CSF), Th1 cytokines (TNF-α and IFN-γ), Th2 cytokines (IL-4 and IL-13), and Th17 cytokines (IL-17A) are shown in controls and patients. Cytokine concentrations, expressed in pg/mL, are shown on the y-axis. *P < 0.05 is consider as significant, **P < 0.005 is consider as significant, and ***P < 0.0005 is consider as significant
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30(12):1591–1601. doi: 10.1002/mds.26424. - DOI - PubMed
    1. Pringsheim T, Jette N, Frolkis A, Steeves TDL. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2014;29(13):1583–1590. doi: 10.1002/mds.25945. - DOI - PubMed
    1. Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523(7560):337–341. doi: 10.1038/nature14432. - DOI - PMC - PubMed
    1. Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M, et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med. 2015;212(7):991–999. doi: 10.1084/jem.20142290. - DOI - PMC - PubMed
    1. Rocha NP, Assis F, Scalzo PL, Vieira ÉLM, Barbosa IG, de Souza MS, et al. Reduced activated T lymphocytes (CD4+CD25+) and plasma levels of cytokines in Parkinson’s disease. Mol Neurobiol. 2018;55(2):1488–1497. doi: 10.1007/s12035-017-0404-y. - DOI - PubMed