Abstract
Nuclear factor of activated T cells (NFAT) was first described almost three decades ago as a Ca 2+/calcineurin-regulated transcription factor in T cells. Since then, a large body of research uncovered the regulation and physiological function of different NFAT homologues in the immune system and many other tissues. In this review, we will discuss novel roles of NFAT in T cells, focusing mainly on its function in humoral immune responses, immunological tolerance, and the regulation of immune metabolism.
Highlights
While all Nuclear factor of activated T cells (NFAT) homologues are activated by Ca2+/calmodulin and calcineurin-mediated dephosphorylation, NFAT1 and NFAT4 were recently shown to require distinct subcellular Ca2+ and IP3 signals for their activation
In induced Treg (iTreg) cells, NFAT binds to CNS1 together with Smad[3] and facilitates T-cell receptor (TCR)- and TGFβ-induced Foxp[3] expression[72,73,78], whereas CNS1 is dispensable for natural Treg (nTreg) cell development[78] (Figure 2C)
We recently showed that CD4+ T cells lacking Stim[1] and Stim[2], and store-operated Ca2+ entry (SOCE) and NFAT activation, failed to undergo this “glycolytic switch” and antigen receptor-induced clonal expansion[68]
Summary
NFAT proteins: key regulators of T-cell development and function. Hogan PG, Chen L, Nardone J, et al.: Transcriptional regulation by calcium, calcineurin, and NFAT. Lopez-Rodríguez C, Aramburu J, Rakeman AS, et al.: NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun. Proc Natl Acad Sci U S A. Müller MR, Rao A: NFAT, immunity and cancer: a transcription factor comes of age. Serfling E, Klein-Hessling S, Palmetshofer A, et al.: NFAT transcription factors in control of peripheral T cell tolerance. Hermann-Kleiter N, Baier G: NFAT pulls the strings during CD4+ T helper cell effector functions.
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