Single-cell RNA Sequencing-Based analysis of diverse ion-channel transcripts across human CD4+ T-cell subsets

Abstract

CD4+ T lymphocytes orchestrate adaptive immunity and diversify into helper and regulatory subsets that are selectively implicated in autoimmune and allergic diseases. Although ion channels are key determinants of lymphocyte activation and homeostasis, their subset-resolved expression patterns in human CD4+ T cells remain incompletely defined. Here, naïve CD4+ T cells were isolated from human peripheral blood mononuclear cells, polarized in vitro into Th1, Th2, Th17, and regulatory T (Treg) cells, and profiled by single-cell RNA sequencing (scRNA-seq). Unsupervised clustering resolved naïve and differentiated states and enabled subset annotation by canonical marker panels. Comparative analysis of an ion-channel/transporter gene panel revealed subset-biased transcript signatures, including differential representation of Ca2+-handling modules and membrane transport genes. Notably, Th2 showed enriched expression of ITPR1, Treg displayed relatively higher STIM2/ORAI3, and Th17 exhibited prominent AQP3 expression, alongside broad detection of core store-operated Ca2+ entry (SOCE) components across subsets. Collectively, these data provide a single-cell transcriptomic resource that delineates ion-transport landscapes across human CD4+ T-cell subset states and nominates candidate ionic regulators for follow-up mechanistic studies. © 2026 Elsevier Inc.