Inflammation and regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of Parkinson’s disease patients

Abstract

Our aim was to identify the differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMC) of Parkinson’s disease (PD) patients and healthy controls by microarray technology and analysis of related molecular pathways by functional annotation. 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 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 PBMC. 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. 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 effort of the immune system to suppress ongoing neuroinflammation.

CDK5 mediated phosphorylation of cytosolic phospholipase A2 regulates its activity and neuroinflammation in Parkinson’s Disease

“…Upregulation in the oxytocin signalling pathway is also seen to increase the expression of cPLA2 and also increase the calcium ion flux inside the cell (Soloff et al, 2000) . Previous studies have shown that activated microglia contributes to the dopaminergic neuron degeneration in substantia nigra of PD patients (Caggiu et al, 2019) (Karaaslan et al, 2021), reports in murine PD models have also shown upregulation in AA signalling , concordant with these findings increased expression of genes encoding pro-inflammatory cytokines and AA signalling and various other key regulators in these pathways has been found in our analyses. Figure7D, shows a proposed model to explains the mechanism of CDK5/p25 mediated cPLA2 activation leading to neuroinflammation.…”

Significant Difference of Immune Cell Fractions and Their Correlations With Differential Expression Genes in Parkinson’s Disease

“…Although no remarkable difference of Tregs fractions was observed in the blood of patients with PD (Cen et al, 2017), others found CD49d + Tregs increased in PD compared to that in HC (Karaaslan et al, 2021). Tregs dysregulation and its impaired function of suppressing the activation of effector T cells were linked to the pathology of PD and disease severity The biological process of the GO enrichment analysis of filtered genes in green and cyan modules, separately.…”

The Contribution of Microglia to Neuroinflammation in Parkinson’s Disease

“…In addition, these cells were observed to preferentially differentiate towards a Th1-reactive state [ 58 ]. Recent PD research also showed differentially expressed genes in peripheral blood mononuclear cells (PBMCs), with patients presenting an elevated abundance of CD49d+ Treg cells, which are known to suppress inflammatory processes [ 59 ]. When investigating the interaction of microglia and peripheral immune cells in PD, a recent study in rats found an important role of infiltrating T cells.…”