RCAN1C is differentially expressed in T helper cell subsets

Abstract

The Ser/Thr-phosphatase calcineurin is a key enzyme of T cell receptor (TcR)-dependent signaling. Endogenous regulatory proteins regulate its activity in T cells. Here, we show that the transcription of RCAN1, coding for the calcineurin inhibitory protein calcipressin 1, is calcineurin/NFAT-dependently upregulated after TcR stimulation. This is mainly due to an increase in the expression levels of the splice variant RCAN1C, as the splice variant RCAN1A remains unchanged. RCAN1C expression is differentially regulated in various CD4+ T helper (TH) cell subpopulations: RCAN1C is stronger upregulated in CD45RO+ memory TH cells compared to CD45RA+ naive TH cells or regulatory T cells. Additionally, memory TH cells show an elevated baseline expression and a prolonged upregulation of RCAN1C transcription upon stimulation. We are discussing how RCAN1 is regulated and which signal transduction pathways and factors might be involved. It remains to be clarified which differentially activated signaling molecules in the selected TH cell subsets cause the diverse RCAN1C expression pattern.