Nuclear factor of activated T cells regulates the expression of interleukin-4 in Th2 cells in an all-or-none fashion [Gene Regulation]

July 17th, 2014 by Koeck, J., Kreher, S., Lehmann, K., Riedel, R., Bardua, M., Lischke, T., Jargosch, M., Haftmann, C., Bendfeldt, H., Hatam, F., Mashreghi, M.-F., Baumgrass, R., Radbruch, A., Chang, H.-D.

Th2 memory lymphocytes have imprinted their Il4 genes epigenetically for expression in dependency of T cell receptor restimulation. However, in a given restimulation, not all Th cells with a memory for IL-4 expression express IL-4. Here we show that in reactivated Th2 cells, the transcription factors NFATc2, NF-kB p65, c-Maf, p300, Brg1, STAT6 and GATA-3 assemble at the Il4 promoter in Th2 cells expressing IL-4 but not in Th2 cells not expressing it. NFATc2 is critical for assembly of this transcription factor complex. Since NFATc2 translocation into the nucleus occurs in an all-or-none fashion, dependent on complete dephosphorylation by calcineurin, NFATc2 controls the frequencies of cells reexpressing Il4, translates analog differences in T cell receptor stimulation into a digital decision for Il4 reexpression, and instructs all reexpressing cells to express the same amount of IL-4. This analog-to-digital conversion may be critical for the immune system to respond to low concentrations of antigens.