scholarly journals Imbalance of circulating Tfh/Tfr cells in patients with Parkinson’s disease

2020 ◽  
Author(s):  
Xiuzhen Zhao ◽  
Tao Jin ◽  
Chao Zheng ◽  
Di Ma ◽  
Ying Zhang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
T Cells ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Serum Concentrations ◽  
B Cell Differentiation ◽  
Peripheral Blood Mononuclear ◽  
Humoral Immune ◽  
Humoral Immune Responses

Abstract Background: Follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are essential for B cell differentiation, germinal center formation, and humoral immune responses. Immunity and inflammation have been thought to be involved in Parkinson’s disease (PD). In this study, we aimed to identify whether circulating Tfh and Tfr (cTfh and cTfr) cells contribute to PD.Methods: Thirty-nine PD patients and 26 health controls (HCs) were enrolled. The numbers of cTfh (CD4+CXCR5+PD-1+) cells and cTfr (CD4+CXCR5+CD25hiCD127low) cells were analyzed via flow cytometry. The serum concentrations of interleukin (IL)-4, IL-10, IL-21, and transforming growth factor (TGF)-β were examined by cytometric bead array.Results: The percentage of cTfh cells among CD4+ T cells in PD patients was significantly higher than that in HCs [3.68% (2.64%–5.70%) vs 1.94% (1.32%–2.99%), P<0.001], while the percentage of cTfr cells among CD4+ T cells in PD patients was slight decreased but without significance [1.05% (0.62%–1.54%) vs 1.3% (0.63%–1.90%), P>0.05]. The percentage of CD19+ B cells in peripheral blood mononuclear cells was significantly lower in PD patients than in HCs [5.35% (4.13%–9.38%) vs 8.68% (5.61%–12.93%), P=0.014]. The serum concentrations of IL-4, IL-10, IL-21, and TGF-β in PD patients did not differ significantly from those in HCs (P>0.05). However, significant positive correlations were found for the serum concentration of IL-21 with H-Y stage (r=0.356, P=0.026) and UPDRS-III score (r=0.347, P=0.030).Conclusions: These results indicate that an imbalance of cTfh and cTfr cells may be involved in the chronic progression of PD, and IL-21 may be a biomarker for monitoring the severity of this disease.

In on the ground floor: T cells respond to α-synuclein in preclinical Parkinson’s disease

2020 ◽  
Vol 12 (544) ◽  
pp. eabb7100
Author(s):  
Albert A. Davis
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
T Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Ground Floor ◽  
Blood Mononuclear Cells ◽  
Early Parkinson’S Disease

Analysis of peripheral blood mononuclear cells demonstrated that α-synuclein–specific T cells are active in preclinical and early Parkinson’s disease.

Identification of Molecular Mechanisms in Parkinson’s Disease Pathogenesis: Significance of Survival and Inflammation Pathways

2020 ◽  
Author(s):  
Zerrin Karaaslan ◽  
Ozlem Timirci Kahraman ◽  
Elif Sanli ◽  
Hayriye Arzu Ergen ◽  
Basar Bilgic ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Functional Annotation ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Neuronal Degeneration ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Rt Pcr ◽  
Peripheral Blood Mononuclear

Abstract Background: Our aim was to identify the differentially expressed genes (DEGs) between Parkinson’s disease (PD) patients and controls by microarray technology and analysis of related molecular pathways by functional annotation. Methods: Thirty PD patients and 30 controls were enrolled. Agilent Human 8X60 K Oligo Microarray was used for gene level expression identification. Gene ontology and pathway enrichment analyses were used for functional annotation of DEGs. Protein-protein interaction analyses were performed with STRING. Expression levels of randomly selected 5 genes among DEGs were quantified by real time quantitative polymerase chain reaction (RT-PCR) for validation. Flow cytometry was done to determine frequency of regulatory T cells (Tregs) in peripheral blood mononuclear cells. Results: A total of 361 DEGs (143 upregulated and 218 downregulated) were identified after GeneSpring analysis. DEGs were involved in 28 biological processes, 12 cellular components and 26 molecular functions. Pathway analyses demonstrated that upregulated genes mainly enriched in p53 (CASP3, TSC2, ATR, MDM4, CCNG1) and PI3K/Akt (IL2RA, IL4R, TSC2, VEGFA, PKN2, PIK3CA, ITGA4, BCL2L11) signaling pathways. TP53 and PIK3CA were identified as most significant hub proteins. Expression profiles obtained by RT-PCR were consistent with microarray findings. PD patients showed increased proportions of CD49d+ Tregs, which correlated with disability scores. Discussion: Survival pathway genes were upregulated putatively to compensate neuronal degeneration. Bioinformatics analysis showed an association between survival and inflammation genes. Increased CD49d+ Treg ratios might signify the attempt of the immune system to suppress ongoing inflammation. Conclusion: Altered functions of Tregs might have an important role in PD pathogenesis and CD49d expression could be a prognostic biomarker of PD.

scholarly journals Selenoprotein T Promotes Proliferation and G1-to-S Transition in SK-N-SH Cells: Implications in Parkinson's Disease

2019 ◽  
Vol 149 (12) ◽  
pp. 2110-2119 ◽  
Author(s):  
Zi-Qiang Shao ◽  
Xiong Zhang ◽  
Hui-Hui Fan ◽  
Xiao-Shuang Wang ◽  
Hong-Mei Wu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Selenoprotein T ◽  
Blood Mononuclear Cells ◽  
6 Hydroxydopamine

ABSTRACT Background Selenium is prioritized to the brain mainly for selenoprotein expression. Selenoprotein T (SELENOT) protects dopaminergic, postmitotic neurons in a mouse model of Parkinson's disease (PD). Objective We hypothesized a proliferative role of SELENOT in neural cells. Methods To assess SELENOT status in PD, sedated male C57BL/6 mice at 10–12 wk of age were injected with 6-hydroxydopamine in neurons, and human peripheral blood mononuclear cells were isolated from 9 healthy subjects (56% men, 68-y-old) and 11 subjects with PD (64% men, 63-y-old). Dopaminergic neural progenitor–like SK-N-SH cells with transient SELENOT overexpression or knockdown were maintained in the presence or absence of the antioxidant N-acetyl-l-cysteine and the calcium channel blocker nimodipine. Cell cycle, proliferation, and signaling parameters were determined by immunoblotting, qPCR, and flow cytometry. Results SELENOT mRNA abundance was increased (P &lt; 0.05) in SK-N-SH cells treated with 1-methyl-4-phenylpyridinium iodide (3.5-fold) and peripheral blood mononuclear cells from PD patients (1.6-fold). Likewise, SELENOT was expressed in tyrosine hydroxylase–positive dopaminergic neurons of 6-hydroxydopamine–injected mice. Knockdown of SELENOT in SK-N-SH cells suppressed (54%; P &lt; 0.05) 5-ethynyl-2′-deoxyuridine incorporation but induced (17–47%; P &lt; 0.05) annexin V–positive cells, CASPASE-3 cleavage, and G1/S cell cycle arrest. SELENOT knockdown and overexpression increased (88–120%; P &lt; 0.05) and reduced (37–42%; P &lt; 0.05) both forkhead box O3 and p27, but reduced (51%; P &lt; 0.05) and increased (1.2-fold; P &lt; 0.05) cyclin-dependent kinase 4 protein abundance, respectively. These protein changes were diminished by nimodipine or N-acetyl-l-cysteine treatment (24 h) at steady-state levels. While the N-acetyl-l-cysteine treatment did not influence the reduction in the amount of calcium (13%; P &lt; 0.05) by SELENOT knockdown, the nimodipine treatment reversed the decreased amount of reactive oxygen species (33%; P &lt; 0.05) by SELENOT overexpression. Conclusions These cellular and mouse data link SELENOT to neural proliferation, expanding our understanding of selenium protection in PD.

Systemic upregulation of CD40 and CD40 ligand mRNA expression in multiple sclerosis

2000 ◽  
Vol 6 (2) ◽  
pp. 61-65 ◽  
Author(s):  
Wen-Xin Huang ◽  
Ping Huang ◽  
Jan Hillert
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Cd40 Ligand ◽  
Autoimmune Response ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Organ Specific

It is increasingly clear that the CD40 and CD40 ligand (CD40L) receptor-ligand pair mediates a crucial activation signal in both cell-mediated and humoral immune responses. Here, we detected mRNA levels of CD40 and CD40L in non-stimulated peripheral blood mononuclear cells in 46 patients with multiple sclerosis (MS) and 46 healthy controls by a competitive RT-PCR procedure allowing quantification without previous culture or antigenic stimulation. The levels of CD40 and CD40L mRNA were markedly increased in MS patients (P <0.0001) compared with healthy controls. There was no difference between clinical MS subgroups or stage of disease. Our findings indicate that, although MS is an organ specific disorder an increased signaling via the CD40 and CD40L pathway may be present at the systemic level. The nature of this upregulation, whether primary or secondary to the organ-specific autoimmune response, is yet to be determined. Since interference with CD40/CD40L is an effective way to interfere with autoimmune model diseases such as experimental autoimmune encephalomyelitis, it may be relevant to investigate further the role of these molecules in the pathogenesis of MS.

Lysosomal alterations in peripheral blood mononuclear cells of Parkinson's disease patients

2015 ◽  
Vol 30 (13) ◽  
pp. 1830-1834 ◽  
Author(s):  
Nikolaos Papagiannakis ◽  
Maria Xilouri ◽  
Christos Koros ◽  
Maria Stamelou ◽  
Roubina Antonelou ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

scholarly journals Transforming Growth Factor β1 Production by CD4+ CD25+ Regulatory T Cells in Peripheral Blood Mononuclear Cells from Healthy Subjects Stimulated with Leishmania guyanensis

2005 ◽  
Vol 73 (9) ◽  
pp. 5908-5914 ◽  
Author(s):  
A. Kariminia ◽  
E. Bourreau ◽  
H. Pascalis ◽  
P. Couppié ◽  
D. Sainte-Marie ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Suppressive Activity ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Leishmania Guyanensis ◽  
Tgf Β1

ABSTRACT Transforming growth factor β (TGF-β) has been shown to be a central immunomodulator used by leishmaniae to escape effective mechanisms of protection in human and murine infections with these parasites. However, all the information is derived from studies of established infection, while little is known about TGF-β production in response to Leishmania stimulation in healthy subjects. In this study, TGF-β1 production was demonstrated in peripheral blood mononuclear cells from healthy subjects never exposed to leishmaniae in response to live Leishmania guyanensis, and the TGF-β1-producing cells were described as a distinct subpopulation of CD4+ CD25+ regulatory T cells. The suppressive properties of CD4+ CD25+ T cells were demonstrated in vitro by their inhibition of production of interleukin 2 (IL-2) and IL-10 by CD4+ CD25− T cells in the presence of either anti-CD3 or L. guyanensis. Although neutralization of TGF-β1 did not reverse the suppressive activity of CD4+ CD25+ T cells activated by anti-CD3, it reversed the suppressive activity of CD4+ CD25+ T cells activated by L. guyanensis. Altogether our data demonstrated that TGF-β1 is involved in the suppressive activity of L. guyanensis-stimulated CD4+ CD25+ T cells from healthy controls.

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