*4.4. The Calcineurin*/*NF-AT Signaling Pathway*

To understand the mechanisms of CNIs, the interaction between intracellular calcineurin and nuclear factor of activated T cells (NF-AT) is important (Figure 1). In resting cells, NF-AT proteins are hyperphosphorylated and are localized in the cytoplasm. On activation, NF-AT proteins undergo rapid dephosphorylation by calcineurin. The dephosphorylated NF-AT proteins then translocate into the nucleus, where they regulate gene transcription. NF-ATs regulate a large number of inducible genes in immune cells, including cytokines, cell-surface receptors, and chemokines [42].

Dephosphorylating NF-AT by calcineurin is a calcium-dependent process, and as soon as the calcium signals cease, it leads to rephosphorylation, initiating NF-AT to return from its active state in the nucleus to its inactive state in the cytoplasm.
