Trpm4 differentially regulates Th1 and Th2 function by altering calcium signaling and NFAT localization.
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Weber KS, Hildner K, Murphy KM, Allen PM
Trpm4 differentially regulates Th1 and Th2 function by altering calcium signaling and NFAT localization.
J Immunol. 2010 Sep 1;185(5):2836-46. doi: 10.4049/jimmunol.1000880. Epub 2010 Jul 23.
- PubMed ID
- 20656926 [ View in PubMed]
- Abstract
Th cell subsets have unique calcium (Ca(2+)) signals when activated with identical stimuli. The regulation of these Ca(2+) signals and their correlation to the biological function of each T cell subset remains unclear. Trpm4 is a Ca(2+)-activated cation channel that we found is expressed at higher levels in Th2 cells compared with Th1 cells. Inhibition of Trpm4 expression increased Ca(2+) 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 Ca(2+) signaling and NFATc1 localization.