Antigenic stimulation of T lymphocytes initiates a complex series of intracellular signal transduction pathways that leads to the expression of a panel of immunoregulatory genes, whose function is critical to the initiation and coordination of the immune response. The multi-subunit nuclear factor of activated T cells (NFAT) transcription factor family plays a pivotal role in this process and is involved in the expression of a number of immunologically important genes. These include the cytokines IL-2, IL-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor, and tumour necrosis factor-alpha, as well as several cell-surface molecules, such as CD40L and FasL. Although originally described in T cells, it is now apparent that NFAT proteins are also expressed in other immune system cells, including B cells, mast cells, basophils and natural killer cells, as well as in a variety of non-immune cell types and tissues, such as skeletal muscle, neurons, heart and adipocytes. However, although NFAT acts as a calcium-dependent transcription factor and serves to couple gene expression to changes in intracellular calcium levels in most cases, NFAT target genes have not been identified in these latter cell types.

NFAT proteins appear to be regulated primarily at the level of their subcellular localisation [PMID:10652349]. They are found exclusively in the cytoplasm of resting T cells, and consist of 2 components: a pre-existing cytoplasmic component that translocates into the nucleus on calcium mobilisation, and an inducible nuclear component comprising members of the activating protein-1 (AP-1) family of transcription factors. In response to antigen receptor signalling, the calcium-regulated phosphatase calcineurin acts directly to dephosphorylate NFAT proteins, causing their rapid translocation from the cytoplasm to the nucleus, where they cooperatively bind their target