The expression and function of nAChRs in human T cells

Abstract

Nicotinic acetylcholine receptors (nAChRs) are known to modulate immune responses, but their specific role in human T cells remains poorly understood. This thesis project aimed to investigate the expression, regulation, and functional roles of nAChRs in human T cells to shed light on the underlying mechanisms of nAChR-mediated immune regulation. Our study utilized two T cell lines, CCRF-CEM and Jurkat, which express various nAChR subunits, including ⍺7, ⍺9, ⍺10, and dup⍺7. The expression of these subunits was characterized using quantitative PCR. Notably, 48-hr mitogen-induced activation of Jurkat cells induced dynamic changes in nAChR subunit gene expression, including the upregulation of dup⍺7 and downregulation of ⍺7, ⍺9, and α10. Pharmacological studies using several nAChR ligands revealed differential effects on cytokine production in Jurkat cells. The ⍺7-selective antagonist, ArIB, hindered the mitogen-induced release of IL-2 and TNF-⍺, suggesting that ⍺7 nAChR inhibition may suppress T cell-mediated immune responses. Overall, this thesis advances the current understanding of nAChR expression and function in human T cells and underscores the complex and cell type-dependent nature of nAChR signaling. These findings provide a foundation for further research into the role of nAChRs in the immune system and potential therapeutic interventions for immune-related disorders.