image: This figure presents the volcano plots for visualizing DEGs (a) and the functional enrichment analyses (b-d) for upregulated and downregulated DEGs in the immune non-responder (INR) group vs. healthy control (HC) group (b), INR group vs. immune responder (IR) group (c), and IR group vs. HC group (d). (a) Blue dots represent downregulated genes, and red dots represent upregulated genes. The x-axis represents the log2 fold change in gene expression, indicating the degree of upregulation (positive values) or downregulation (negative values). The y-axis represents the -log10 of the adjusted P-value, with higher values indicating greater statistical significance. (b-d) The x-axis shows the enriched terms (biological processes, cellular components, molecular functions, or pathways), and the y-axis represents the -log10 of the adjusted P-value, indicating the significance of enrichment. DEGs, differentially expressed genes; HC, healthy control; IR, immune responder; INR, immune non-responder.
Credit: ong Zhang, Zhen Li, Yang Zhang, Jiahao Ji
Background and objectives
Incomplete immune reconstitution is characterized by chronic immune activation and systemic inflammation, which are not fully reversed by antiretroviral therapy. Dihydroartemisinin (DHA) has demonstrated anti-inflammatory and immunosuppressive properties, which may benefit individuals with incomplete immune reconstitution. This study aimed to investigate the biological mechanisms underlying incomplete immune reconstitution and evaluate the therapeutic potential of DHA in modulating immune activation in immunological non-responders (INRs). This study aimed to investigate the biological mechanisms underlying incomplete immune reconstitution and evaluate the therapeutic potential of DHA in modulating immune activation in immunological non-responders (INRs).
Methods
RNA sequencing data (GSE106792) was retrieved from the Gene Expression Omnibus database. R software and Bioconductor packages were used to identify differentially expressed genes (DEGs) among INRs, immune responders (IRs), and healthy controls (HCs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, along with protein-protein interaction (PPI) network construction, were performed. Potential DHA-binding proteins were predicted using the STITCH server and molecular docking studies. Validation experiments were conducted on peripheral blood mononuclear cells from 18 INRs. Cells were treated with varying concentrations of DHA, and CD4+ and CD8+ T cell activation markers (CD38 and HLA-DR) were measured via flow cytometry.
Results
Enrichment and PPI network analysis identified 119, 56, and 189 DEGs in the INR vs. HC, INR vs. IR, and IR vs. HC comparisons, respectively. Enrichment and PPI analyses showed that DEGs were mainly involved in immune response pathways. DHA was predicted to interact with multiple target proteins, indicating anti-inflammatory effects. In vitro, DHA significantly reduced the frequency of CD38− HLA-DR+ CD4+ T cells and CD38+ HLA-DR+ CD8+ T cells at 1,000 µM and 500 µM compared to the control.
Conclusions
This study provides insights into the biological mechanisms underlying incomplete immune reconstitution and supports DHA’s potential as a therapeutic agent. DHA effectively inhibits T cell activation in INRs, presenting a novel and promising treatment strategy.
Full text
https://www.xiahepublishing.com/2572-5505/JERP-2024-00014
The study was recently published in the Journal of Exploratory Research in Pharmacology.
Journal of Exploratory Research in Pharmacology (JERP) publishes original innovative exploratory research articles, state-of-the-art reviews, editorials, short communications that focus on novel findings and the most recent advances in basic and clinical pharmacology, covering topics from drug research, drug development, clinical trials and application.
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Journal
Journal of Exploratory Research in Pharmacology
Article Title
Dihydroartemisinin Inhibits T Cell Activation in People Living with HIV with Incomplete Immune Reconstitution In Vitro
Article Publication Date
30-Dec-2024