Th cell subsets have unique calcium (Ca2+) signals when activated with identical stimuli. The regulation of these Ca2+ signals and their correlation to the biological function of each T cell subset remains unclear. Trpm4 is a Ca2+-activated cation channel that we found is expressed at higher levels in Th2 cells compared with Th1 cells. Inhibition of Trpm4 expression increased Ca2+ influx and oscillatory levels in Th2 cells and decreased influx and oscillations in Th1 cells. This inhibition of Trpm4 expression also significantly altered T cell cytokine production and motility. Our experiments revealed that decreasing Trpm4 levels divergently regulates nuclear localization of NFATc1. Consistent with this, gene profiling did not show Trpm4-dependent transcriptional regulation, and T-bet and GATA-3 levels remain identical. Thus, Trpm4 is expressed at different levels in Th cells and plays a distinctive role in T cell function by differentially regulating Ca2+ signaling and NFATc1 localization.

Original languageEnglish
Pages (from-to)2836-2846
Number of pages11
JournalJournal of Immunology
Issue number5
StatePublished - Sep 1 2010


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