NFAT1 transcription factor in dendritic cells is required to modulate T helper cell differentiation

Abstract

The NFAT family of transcription factors plays a central role in the regulation of cytokine gene expression during the immune response. NFAT functions have been extensively explored in lymphocyte activation and differentiation, but the involvement of NFAT proteins in dendritic cells (DCs) is still not well known. Here, we investigated the role of the NFAT1 transcription factor in murine DCs. Initially, we demonstrated by western blot that the NFAT1 protein is present in splenic DCs and is rapidly activated upon calcium influx. We then used NFAT1-deficient mice (NFAT1−/−) to investigate whether NFAT1 influences the ability of DCs to induce Th differentiation. Our data demonstrated that NFAT1−/− DCs showed an increased capacity to differentiate CD4 T cells to the Th1 phenotype. CD4 cells that were primed in vitro with NFAT1−/− DCs had increased IFN-γ production. The same results were observed when the CD4 cells were primed in vivo through the sensitization of NFAT1−/− mice with ovalbumin. Furthermore, our results demonstrated that the cytokine IL-12 is one of the factors involved in this process because its production is increased in NFAT1−/− mice, and neutralizing anti-IL-12 antibodies almost completely eliminated the IFN-γ production. These results demonstrated that the NFAT1 transcription factor regulates specific functions in DCs that are involved in CD4 differentiation, suggesting that the inhibition of NFAT1 in DCs may be used as a therapy to modulate specific immune responses.