Aberrantly Expressed Long Non-Coding RNAs In CD8⁺ T Cells Response to Active Tuberculosis

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in various human diseases.
• Dysregulated lncRNA expression is implicated in immune system disorders.
• CD8+ T cells play a critical role in cell-mediated immunity against infectious diseases like tuberculosis.

Purpose of the Study:

• To investigate the lncRNA expression profile in CD8+ T cells from patients with active tuberculosis (TB).
• To identify potential lncRNAs associated with CD8+ T cell dysfunction in active TB.
• To explore the functional implications of differentially expressed lncRNAs and mRNAs in TB.

Main Methods:

• Microarray analysis to profile lncRNA and mRNA expression in CD8+ T cells.
• Bioinformatic analysis (change prediction) to infer functional roles of deregulated mRNAs.
• Real-time quantitative PCR (RT-qPCR) for validation of microarray findings.

Main Results:

• Significant differential expression of 328 lncRNAs and 356 mRNAs in active TB CD8+ T cells compared to healthy controls.
• Upregulated mRNAs were enriched in pathways like cAMP signaling, calcium signaling, and TGF-beta signaling.
• Downregulated mRNAs were associated with antigen processing, presentation, and natural killer cell-mediated cytotoxicity.
• Decreased heme oxygenase 1 (HMOX1) and upregulated its nearby lincRNA XLOC_014219 were observed in TB CD8+ T cells.

Conclusions:

• This study presents the first comprehensive lncRNA expression profile in active TB CD8+ T cells.
• Aberrantly expressed lncRNAs may contribute to CD8+ T cell dysfunction and the pathophysiology of active TB.
• Identified lncRNAs offer potential biomarkers and therapeutic targets for active TB, warranting further functional investigation.