Transcriptomic Analysis Reveals Receptor Subclass-Specific Immune Regulation of CD8⁺ T Cells by Opioids.

ABSTRACT: Opioid peptides are released at sites of injury, and their cognate G protein-coupled opioid receptors (OR) are expressed on immune cells. Exposure of human circulating CD8⁺ T cells to selective OR agonists differentially regulates thousands of genes. Gene set enrichment analysis reveals that μ-OR more strongly regulates cellular processes than δ-OR. In TCR naive T cells, triggering μ-OR exhibits stimulatory and inhibitory patterns, yet when administered prior to TCR cross-linking, a μ-OR agonist inhibits activation. μ-OR, but not δ-OR, signaling is linked to upregulation of lipid, cholesterol, and steroid hormone biosynthesis, suggesting lipid regulation is a mechanism for immune suppression. Lipid rafts are cholesterol-rich, liquid-ordered membrane domains that function as a ne

SUBMITTER: Mazahery C 

PROVIDER: S-EPMC8236285 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature