Nicotinic acetylcholine receptor signaling regulates cytokine production in Jurkat T cells

Nicotinic acetylcholine receptors (nAChRs) regulate immune cell functions, yet their expression patterns and roles in human T cells remain incompletely defined. The immunomodulatory effects of α7 nAChR signaling in human immune cells is complicated by the presence of the human-specific duplicated α7 (dupα7) subunit. Here, we investigated the expression and function of nAChRs in human Jurkat T cells, focusing on α7, dupα7, α9, and α10. Quantitative PCR revealed transcripts for all four subunits. Mitogenic stimulation with PMA, ionomycin, and ConA significantly downregulated α7, α9, and α10 expression while upregulating dupα7, suggesting dynamic remodeling of receptor composition during T cell activation. Functional assays showed that α7 antagonism with ArIB[V11L,V16D] strongly suppressed mitogen-induced IL-2 and TNF-α secretion, while nicotine pretreatment produced more modest reductions. Flow cytometry confirmed a decreased frequency of IL-2+ cells following treatment with nicotine or nAChR antagonists. These findings establish Jurkat cells as a tractable model for studying nAChR signaling in human T cells. Our results demonstrate that α7-containing nAChRs positively regulate cytokine production, while dupα7 expression increases during activation and may act as a negative regulator of α7 function. Together, these data highlight nAChRs as key modulators of T cell activity and identify α7 and dupα7 as potential therapeutic targets for regulating adaptive immunity.