Background: The NFAT family transcription factors play crucial roles in T cell functions. Recently, NFAT has been implicated in the production of an inflammatory cytokine, IL-17A; however, functional differences among NFAT members in IL-17A synthesis have not been elucidated. In this study, the relative contribution of NFAT1 and NFAT2 to IL-17A expression in human T cells was investigated. Methods: NFAT1 and NFAT2 were introduced in human cord blood CD4+ T cells by a lentiviral transduction system. Then, the expression of IL-17A mRNA was determined by quantitative real-time RT-PCR. The transient effects of NFAT1 and NFAT2 on IL-17A expression in Jurkat-Tag cells were also investigated. Results: Stimulation-induced expression of IL-17A in human CD4+ T cells was augmented by the introduction of NFAT1 and more vigorously, NFAT2. IL-17A expression in Jurkat-Tag cells was also enhanced by NFAT1, whereas it was not affected by NFAT2. Conclusion: NFAT1 and NFAT2 facilitated IL-17A expression in human T cells, though distinct mechanisms might be involved in these effects.

1.
Hogan PG, Chen L, Nardone J, Rao A: Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev 2003;17:2205–2232.
[PubMed]
2.
Serfling E, Berberich-Siebelt F, Chuvpilo S, Jankevics E, Klein-Hessling S, Twardzik T, Avots A: The role of NF-AT transcription factors in T cell activation and differentiation. Biochim Biophys Acta 2000;1498:1–18.
3.
Kaminuma O: Selective inhibitors of nuclear factor of activated T cells: potential therapeutic drugs for the treatment of immunological and inflammatory diseases. Inflamm Allergy Drug Targets 2008;7:35–40.
[PubMed]
4.
Clipstone NA, Crabtree GR: Identification of calcineurin as a key signaling enzyme in T-lymphocyte activation. Nature 1992;357:695–697.
[PubMed]
5.
Fruman DA, Klee CB, Bierer BE, Burakoff SJ: Calcineurin phosphatase activity in T lymphocytes is inhibited by FK506 and cyclosporin A. Proc Natl Acad Sci USA 1992;89:3686–3690.
[PubMed]
6.
Crome SQ, Wang AY, Levings MK: Translational mini-review series on Th17 cells: function and regulation of human T helper 17 cells in health and disease. Clin Exp Immunol 2009;159:109–119.
7.
Strzepa A, Szczepanik M: IL-17-expressing cells as a potential therapeutic target for treatment of immunological disorders. Pharmacol Rep 2011;63:30–44.
8.
Onishi RM, Gaffen SL: Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease. Immunology 2010;129:311–321.
9.
Liu XK, Lin X, Gaffen SL: Crucial role for nuclear factor of activated T cells in T cell receptor-mediated regulation of human interleukin-17. J Biol Chem 2004;279:52762–52771.
10.
Hirahara K, Ghoreschi K, Laurence A, Yang XP, Kanno Y, O’Shea JJ: Signal transduction pathways and transcriptional regulation in Th17 cell differentiation. Cytokine Growth Factor Rev 2010;21:425–434.
11.
Weigmann B, Lehr HA, Yancopoulos G, Valenzuela D, Murphy A, Stevens S, Schmidt J, Galle PR, Rose-John S, Neurath MF: The transcription factor NFATc2 controls IL-6-dependent T cell activation in experimental colitis. J Exp Med 2008;205:2099–2110.
12.
Ghosh S, Koralov SB, Stevanovic I, Sundrud MS, Sasaki Y, Rajewsky K, Rao A, Muller MR: Hyperactivation of nuclear factor of activated T cells 1 (NFAT1) in T cells attenuates severity of murine autoimmune encephalomyelitis. Proc Natl Acad Sci USA 2010;107:15169–15174.
13.
Kaminuma O, Kitamura F, Kitamura N, Hiroi T, Miyoshi H, Miyawaki A, Miyatake S: Differential contribution of NFATc2 and NFATc1 to TNF-alpha gene expression in T cells. J Immunol 2008;180:319–326.
[PubMed]
14.
Kaminuma O, Kitamura F, Miyatake S, Yamaoka K, Miyoshi H, Inokuma S, Tatsumi H, Nemoto S, Kitamura N, Mori A, Hiroi T: T-box 21 transcription factor is responsible for distorted T(H)2 differentiation in human peripheral CD4+ T cells. J Allergy Clin Immunol 2009;123:813–823.e3.
[PubMed]
15.
Napolitani G, Acosta-Rodriguez EV, Lanzavecchia A, Sallusto F: Prostaglandin E2 enhances Th17 responses via modulation of IL-17 and IFN-gamma production by memory CD4+ T cells. Eur J Immunol 2009;39:1301–1312.
16.
Pham LV, Tamayo AT, Li C, Bueso-Ramos C, Ford RJ: An epigenetic chromatin remodeling role for NFATc1 in transcriptional regulation of growth and survival genes in diffuse large B-cell lymphomas. Blood 2010;116:3899–3906.
You do not currently have access to this content.