Poster abstracts

Poster number 85 submitted by Claire Mazahery

Opioid-induced long noncoding transcriptome of human CD8+ T cells reveals opioid receptor subclass specific responses

Claire Mazahery (Pathology, Case Western Reserve University), Braulio Llorens (Molecular Biology and Microbiology, Case Western Reserve University), Saba Valadkhan (Molecular Biology and Microbiology, Case Western Reserve University), Alan D. Levine (Pathology, Molecular Biology and Microbiology, Case Western Reserve University)

Abstract:
Endogenous opioid peptides are released at sites of injury, and their cognate G-protein coupled opioid receptors (OR) are expressed on immune cells. Conflicting reports attribute immunostimulatory (opioids activate innate immune cells) and immunosuppressive (opioid users have elevated infection risk) activity to opioids. Intravenous drug use transmits viral infections, making the study of CD8+ T cells timely. From a cohort of methadone patients, we found that chronic opioid use disrupts CD8+ T cell subset balance, with decreases in T Effector Memory RA+ cells. Our findings from ex vivo T cell culture suggest that transcriptional mechanisms regulate the outcome from opioid receptor ligation, by modifying the coding and non-coding transcriptome. When T cells are activated through the T cell receptor (TCR) after 18 hours of opioid exposure, the noncoding RNA profile differs substantially from that seen with TCR stimulation without opioid pre-exposure. Globally, μ-OR signaling robustly inhibits or upregulates expression of lncRNAs, while δ-OR signaling has modest effects on expression. Compared to the response of protein coding genes, noncoding RNA expression showed more OR subclass specific regulation. Additionally, we identified >30 unannotated lncRNAs regulated by opioids ex vivo. We are silencing and overexpressing the noncoding RNAs we identified to define their ability to regulate OR specific responses. We are also investigating the contribution of these non-coding RNAs to the immunostimulatory and immunosuppressive perturbations observed in opioid users by contrasting lncRNA expression and activity in CD4 vs. CD8 T cells.

Keywords: noncoding transcriptome , human CD8+ T cells , opioid