CoChat
Sign Up
Cited by 191Signaling Pathways in DiseaseT-cell and B-cell ImmunologyNuclear Receptors and Signaling

NFAT control of immune function: New Frontiers for an Abiding Trooper

Open access
Vaeth, Martin, Feske, Stefan·2018·F1000Research
DOI 10.12688/f1000research.13426.1PMC PMC5840618
Open this paper in CoChat — free accountOpen PDF

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.12688/f1000research.13426.1

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • NFAT has been considered to be an immune-related protein and expressed in T cells and macrophages.

    “NFAT has been considered to be an immune-related protein and expressed in T cells and macrophages (66).”

    From LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies (2020) · cites this paper as [66]

    The Introduction identifies NFAT as a transcription-factor family first found in activated T cells, and the section on peripheral immune tolerance describes its roles in immune function. The passages in our copy do not establish the claim that NFAT is expressed in macrophages (searched: macrophage, macrophages NFAT expression). (LLM, conf=0.85)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 119

  1. [1]Shaw JP Utz PJ Durand DB: Identification of a putative regulator of early T cell activation genes. Science. 1988; 241(4862): 202– 5. 10.1126/science.3260404 3260404 F1000 Recommendation · DOI
  2. [2]Serfling E Barthelmäs R Pfeuffer I: Ubiquitous and lymphocyte-specific factors are involved in the induction of the mouse interleukin 2 gene in T lymphocytes. EMBO J. 1989; 8(2): 465– 73. 2542017 PMC400828 F1000 Recommendation
  3. [3]McCaffrey PG Luo C Kerppola TK: Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. Science. 1993; 262(5134): 750– 54. 10.1126/science.8235597 8235597 F1000 Recommendation · DOI
  4. [4]Northrop JP Ho SN Chen L: NF-AT components define a family of transcription factors targeted in T-cell activation. Nature. 1994; 369(6480): 497– 502. 10.1038/369497a0 8202141 F1000 Recommendation · DOI
  5. [5]Loh C Shaw KT Carew J: Calcineurin binds the transcription factor NFAT1 and reversibly regulates its activity. J Biol Chem. 1996; 271(18): 10884– 91. 10.1074/jbc.271.18.10884 8631904 · DOI
  6. [6]Luo C Burgeon E Carew JA: Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes. Mol Cell Biol. 1996; 16(7): 3955– 66. 10.1128/MCB.16.7.3955 8668213 PMC231392 · DOI
  7. [7]Luo C Shaw KT Raghavan A: Interaction of calcineurin with a domain of the transcription factor NFAT1 that controls nuclear import. Proc Natl Acad Sci U S A. 1996; 93(17): 8907– 12. 10.1073/pnas.93.17.8907 8799126 PMC38567 · DOI
  8. [8]Flanagan WM Corthésy B Bram RJ: Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. Nature. 1991; 352(6338): 803– 7. 10.1038/352803a0 1715516 · DOI
  9. [9]Clipstone NA Crabtree GR: Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation. Nature. 1992; 357(6380): 695– 7. 10.1038/357695a0 1377362 · DOI
  10. [10]Serafini AT Lewis RS Clipstone NA: Isolation of mutant T lymphocytes with defects in capacitative calcium entry. Immunity. 1995; 3(2): 239– 50. 10.1016/1074-7613(95)90093-4 7648396 · DOI
  11. [11]Crabtree GR Olson EN: NFAT signaling: choreographing the social lives of cells. Cell. 2002; 109(Suppl): S67– 79. 10.1016/S0092-8674(02)00699-2 11983154 · DOI · Paper page
  12. [12]Randak C Brabletz T Hergenröther M: Cyclosporin A suppresses the expression of the interleukin 2 gene by inhibiting the binding of lymphocyte-specific factors to the IL-2 enhancer. EMBO J. 1990; 9(8): 2529– 36. 2369902 PMC552283
  13. [13]Loh C Carew JA Kim J: T-cell receptor stimulation elicits an early phase of activation and a later phase of deactivation of the transcription factor NFAT1. Mol Cell Biol. 1996; 16(7): 3945– 54. 10.1128/MCB.16.7.3945 8668212 PMC231391 · DOI
  14. [14]Macian F: NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol. 2005; 5(6): 472– 84. 10.1038/nri1632 15928679 · DOI
  15. [15]Hogan PG Chen L Nardone J: Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 2003; 17(18): 2205– 32. 10.1101/gad.1102703 12975316 · DOI · Paper page
  16. [16]Lopez-Rodríguez C Aramburu J Rakeman AS: NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun. Proc Natl Acad Sci U S A. 1999; 96(13): 7214– 9. 10.1073/pnas.96.13.7214 10377394 PMC22056 · DOI
  17. [17]Mognol GP Carneiro FR Robbs BK: Cell cycle and apoptosis regulation by NFAT transcription factors: new roles for an old player. Cell Death Dis. 2016; 7: e2199. 10.1038/cddis.2016.97 27100893 PMC4855676 · DOI
  18. [18]Müller MR Rao A: NFAT, immunity and cancer: a transcription factor comes of age. Nat Rev Immunol. 2010; 10(9): 645– 56. 10.1038/nri2818 20725108 · DOI
  19. [19]Serfling E Klein-Hessling S Palmetshofer A: NFAT transcription factors in control of peripheral T cell tolerance. Eur J Immunol. 2006; 36(11): 2837– 43. 10.1002/eji.200536618 17039563 · DOI
  20. [20]Hermann-Kleiter N Baier G: NFAT pulls the strings during CD4 + T helper cell effector functions. Blood. 2010; 115(15): 2989– 97. 10.1182/blood-2009-10-233585 20103781 · DOI · Paper page
  21. [21]Feske S: Calcium signalling in lymphocyte activation and disease. Nat Rev Immunol. 2007; 7(9): 690– 702. 10.1038/nri2152 17703229 · DOI · Paper page
  22. [22]Vaeth M Yang J Yamashita M: ORAI2 modulates store-operated calcium entry and T cell-mediated immunity. Nat Commun. 2017; 8: 14714. 10.1038/ncomms14714 28294127 PMC5355949 · DOI
  23. [23]Prakriya M Feske S Gwack Y: Orai1 is an essential pore subunit of the CRAC channel. Nature. 2006; 443(7108): 230– 3. 10.1038/nature05122 16921383 · DOI
  24. [24]Hogan PG Lewis RS Rao A: Molecular basis of calcium signaling in lymphocytes: STIM and ORAI. Annu Rev Immunol. 2010; 28: 491– 533. 10.1146/annurev.immunol.021908.132550 20307213 PMC2861828 · DOI
  25. [25]Okamura H Garcia-Rodriguez C Martinson H: A conserved docking motif for CK1 binding controls the nuclear localization of NFAT1. Mol Cell Biol. 2004; 24(10): 4184– 95. 10.1128/MCB.24.10.4184-4195.2004 15121840 PMC400483 · DOI
  26. [26]Okamura H Aramburu J García-Rodríguez C: Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity. Mol Cell. 2000; 6(3): 539– 50. 10.1016/S1097-2765(00)00053-8 11030334 · DOI
  27. [27]Huang GN Huso DL Bouyain S: NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins. Science. 2008; 319(5862): 476– 81. 10.1126/science.1151227 18218901 PMC3602998 · DOI
  28. [28]Willingham AT Orth AP Batalov S: A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science. 2005; 309(5740): 1570– 3. 10.1126/science.1115901 16141075 · DOI
  29. [29]Liu Z Lee J Krummey S: The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease. Nat Immunol. 2011; 12(11): 1063– 70. 10.1038/ni.2113 21983832 PMC4140245 · DOI
  30. [30]Beals CR Sheridan CM Turck CW: Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3. Science. 1997; 275(5308): 1930– 4. 10.1126/science.275.5308.1930 9072970 · DOI
  31. [31]Arron JR Winslow MM Polleri A: NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature. 2006; 441(7093): 595– 600. 10.1038/nature04678 16554754 · DOI · Paper page
  32. [32]Kar P Nelson C Parekh AB: Selective activation of the transcription factor NFAT1 by calcium microdomains near Ca 2+ release-activated Ca 2+ (CRAC) channels. J Biol Chem. 2011; 286(17): 14795– 803. 10.1074/jbc.M111.220582 21325277 PMC3083208 · DOI
  33. [33]Kar P Mirams GR Christian HC: Control of NFAT Isoform Activation and NFAT-Dependent Gene Expression through Two Coincident and Spatially Segregated Intracellular Ca 2+ Signals. Mol Cell. 2016; 64(4): 746– 59. 10.1016/j.molcel.2016.11.011 27863227 PMC5128683 F1000 Recommendation · DOI
  34. [34]Kar P Parekh AB: Distinct spatial Ca 2+ signatures selectively activate different NFAT transcription factor isoforms. Mol Cell. 2015; 58(2): 232– 43. 10.1016/j.molcel.2015.02.027 25818645 PMC4405353 F1000 Recommendation · DOI
  35. [35]Kim JH Kim K Youn BU: RANKL induces NFATc1 acetylation and stability via histone acetyltransferases during osteoclast differentiation. Biochem J. 2011; 436(2): 253– 62. 10.1042/BJ20110062 21413932 · DOI
  36. [36]Wu W Misra RS Russell JQ: Proteolytic regulation of nuclear factor of activated T (NFAT) c2 cells and NFAT activity by caspase-3. J Biol Chem. 2006; 281(16): 10682– 90. 10.1074/jbc.M511759200 16455648 · DOI
  37. [37]Nayak A Glöckner-Pagel J Vaeth M: Sumoylation of the transcription factor NFATc1 leads to its subnuclear relocalization and interleukin-2 repression by histone deacetylase. J Biol Chem. 2009; 284(16): 10935– 46. 10.1074/jbc.M900465200 19218564 PMC2667779 · DOI
  38. [38]Terui Y Saad N Jia S: Dual role of sumoylation in the nuclear localization and transcriptional activation of NFAT1. J Biol Chem. 2004; 279(27): 28257– 65. 10.1074/jbc.M403153200 15117942 · DOI
  39. [39]Vihma H Timmusk T: Sumoylation regulates the transcriptional activity of different human NFAT isoforms in neurons. Neurosci Lett. 2017; 653: 302– 7. 10.1016/j.neulet.2017.05.074 28595951 · DOI
  40. [40]Marangoni F Murooka TT Manzo T: The transcription factor NFAT exhibits signal memory during serial T cell interactions with antigen-presenting cells. Immunity. 2013; 38(2): 237– 49. 10.1016/j.immuni.2012.09.012 23313588 PMC3582823 · DOI
  41. [41]Cho J Kim HO Kim KS: Unique features of naive CD8 + T cell activation by IL-2. J Immunol. 2013; 191(11): 5559– 73. 10.4049/jimmunol.1302293 24166977 · DOI
  42. [42]Patra AK Avots A Zahedi RP: An alternative NFAT-activation pathway mediated by IL-7 is critical for early thymocyte development. Nat Immunol. 2013; 14(2): 127– 35. 10.1038/ni.2507 23263556 F1000 Recommendation · DOI
  43. [43]Barlic J McDermott DH Merrell MN: Interleukin (IL)-15 and IL-2 reciprocally regulate expression of the chemokine receptor CX3CR1 through selective NFAT1- and NFAT2-dependent mechanisms. J Biol Chem. 2004; 279(47): 48520– 34. 10.1074/jbc.M406978200 15347678 · DOI
  44. [44]Rudolf R Busch R Patra AK: Architecture and expression of the nfatc1 gene in lymphocytes. Front Immunol. 2014; 5: 21. 10.3389/fimmu.2014.00021 24550910 PMC3909943 · DOI
  45. [45]Hock M Vaeth M Rudolf R: NFATc1 induction in peripheral T and B lymphocytes. J Immunol. 2013; 190(5): 2345– 53. 10.4049/jimmunol.1201591 23365084 · DOI
  46. [46]Serfling E Avots A Klein-Hessling S: NFATc1/αA: The other Face of NFAT Factors in Lymphocytes. Cell Commun Signal. 2012; 10(1): 16. 10.1186/1478-811X-10-16 22764736 PMC3464794 · DOI
  47. [47]Chuvpilo S Avots A Berberich-Siebelt F: Multiple NF-ATc isoforms with individual transcriptional properties are synthesized in T lymphocytes. J Immunol. 1999; 162(12): 7294– 301. 10358178
  48. [48]Chuvpilo S Jankevics E Tyrsin D: Autoregulation of NFATc1/A expression facilitates effector T cells to escape from rapid apoptosis. Immunity. 2002; 16(6): 881– 95. 10.1016/S1074-7613(02)00329-1 12121669 · DOI
  49. [49]Chuvpilo S Zimmer M Kerstan A: Alternative polyadenylation events contribute to the induction of NF-ATc in effector T cells. Immunity. 1999; 10(2): 261– 9. 10.1016/S1074-7613(00)80026-6 10072078 · DOI
  50. [50]Serfling E Chuvpilo S Liu J: NFATc1 autoregulation: a crucial step for cell-fate determination. Trends Immunol. 2006; 27(10): 461– 9. 10.1016/j.it.2006.08.005 16931157 · DOI
  51. [51]Feske S Giltnane J Dolmetsch R: Gene regulation mediated by calcium signals in T lymphocytes. Nat Immunol. 2001; 2(4): 316– 24. 10.1038/86318 11276202 · DOI
  52. [52]Crotty S: Follicular helper CD4 T cells (T FH). Annu Rev Immunol. 2011; 29: 621– 63. 10.1146/annurev-immunol-031210-101400 21314428 · DOI · Paper page
  53. [53]Crotty S: T follicular helper cell differentiation, function, and roles in disease. Immunity. 2014; 41(4): 529– 42. 10.1016/j.immuni.2014.10.004 25367570 PMC4223692 · DOI · Paper page
  54. [54]Vaeth M Müller G Stauss D: Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression. J Exp Med. 2014; 211(3): 545– 61. 10.1084/jem.20130604 24590764 PMC3949566 · DOI
  55. [55]Bhattacharyya S Deb J Patra AK: NFATc1 affects mouse splenic B cell function by controlling the calcineurin--NFAT signaling network. J Exp Med. 2011; 208(4): 823– 39. 10.1084/jem.20100945 21464221 PMC3135343 · DOI
  56. [56]Yoshida H Nishina H Takimoto H: The transcription factor NF-ATc1 regulates lymphocyte proliferation and Th2 cytokine production. Immunity. 1998; 8(1): 115– 24. 10.1016/S1074-7613(00)80464-1 9462517 · DOI
  57. [57]Muhammad K Alrefai H Marienfeld R: NF-κB factors control the induction of NFATc1 in B lymphocytes. Eur J Immunol. 2014; 44(11): 3392– 402. 10.1002/eji.201444756 25179582 · DOI
  58. [58]Matsumoto M Fujii Y Baba A: The calcium sensors STIM1 and STIM2 control B cell regulatory function through interleukin-10 production. Immunity. 2011; 34(5): 703– 14. 10.1016/j.immuni.2011.03.016 21530328 · DOI
  59. [59]Vaeth M Eckstein M Shaw PJ: Store-Operated Ca 2+ Entry in Follicular T Cells Controls Humoral Immune Responses and Autoimmunity. Immunity. 2016; 44(6): 1350– 64. 10.1016/j.immuni.2016.04.013 27261277 PMC4917422 · DOI
  60. [60]Martinez GJ Hu JK Pereira RM: Cutting Edge: NFAT Transcription Factors Promote the Generation of Follicular Helper T Cells in Response to Acute Viral Infection. J Immunol. 2016; 196(5): 2015– 9. 10.4049/jimmunol.1501841 26851216 PMC4761453 · DOI
  61. [62]Tsytsykova AV Tsitsikov EN Geha RS: The CD40L promoter contains nuclear factor of activated T cells-binding motifs which require AP-1 binding for activation of transcription. J Biol Chem. 1996; 271(7): 3763– 70. 10.1074/jbc.271.7.3763 8631992 · DOI
  62. [63]Kim HP Korn LL Gamero AM: Calcium-dependent activation of interleukin-21 gene expression in T cells. J Biol Chem. 2005; 280(26): 25291– 7. 10.1074/jbc.M501459200 15879595 · DOI
  63. [64]Monticelli S Rao A: NFAT1 and NFAT2 are positive regulators of IL-4 gene transcription. Eur J Immunol. 2002; 32(10): 2971– 8. 10.1002/1521-4141(2002010)32:10<2971::AID-IMMU2971>3.0.CO;2-G 12355451 · DOI
  64. [65]Koch S Reppert S Finotto S: NFATc1 deletion in T lymphocytes inhibits the allergic trait in a murine model of asthma. Clin Exp Allergy. 2015; 45(8): 1356– 66. 10.1111/cea.12493 25640055 · DOI
  65. [66]Man K Miasari M Shi W: The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells. Nat Immunol. 2013; 14(11): 1155– 65. 10.1038/ni.2710 24056747 · DOI
  66. [67]Mahnke J Schumacher V Ahrens S: Interferon Regulatory Factor 4 controls T H1 cell effector function and metabolism. Sci Rep. 2016; 6: 35521. 10.1038/srep35521 27762344 PMC5071867 · DOI
  67. [68]Vaeth M Maus M Klein-Hessling S: Store-Operated Ca 2+ Entry Controls Clonal Expansion of T Cells through Metabolic Reprogramming. Immunity. 2017; 47(4): 664– 679.e6. 10.1016/j.immuni.2017.09.003 29030115 PMC5683398 · DOI
  68. [69]Bandukwala HS Wu Y Feuerer M: Structure of a domain-swapped FOXP3 dimer on DNA and its function in regulatory T cells. Immunity. 2011; 34(4): 479– 91. 10.1016/j.immuni.2011.02.017 21458306 PMC3085397 · DOI
  69. [70]Li X Liang Y LeBlanc M: Function of a Foxp3 cis-element in protecting regulatory T cell identity. Cell. 2014; 158(4): 734– 48. 10.1016/j.cell.2014.07.030 25126782 PMC4151505 · DOI
  70. [71]Lozano T Villanueva L Durántez M: Inhibition of FOXP3/NFAT Interaction Enhances T Cell Function after TCR Stimulation. J Immunol. 2015; 195(7): 3180– 9. 10.4049/jimmunol.1402997 26324768 · DOI
  71. [72]Tone Y Furuuchi K Kojima Y: Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nat Immunol. 2008; 9(2): 194– 202. 10.1038/ni1549 18157133 · DOI · Paper page
  72. [73]Vaeth M Schliesser U Müller G: Dependence on nuclear factor of activated T-cells (NFAT) levels discriminates conventional T cells from Foxp3 + regulatory T cells. Proc Natl Acad Sci U S A. 2012; 109(40): 16258– 63. 10.1073/pnas.1203870109 22991461 PMC3479579 · DOI
  73. [74]Wu Y Borde M Heissmeyer V: FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell. 2006; 126(2): 375– 87. 10.1016/j.cell.2006.05.042 16873067 F1000 Recommendation · DOI
  74. [75]Alrefai H Muhammad K Rudolf R: NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells. Nat Commun. 2016; 7: 11724. 10.1038/ncomms11724 27222343 PMC4894959 · DOI
  75. [76]Rudensky AY: Regulatory T cells and Foxp3. Immunol Rev. 2011; 241(1): 260– 8. 10.1111/j.1600-065X.2011.01018.x 21488902 PMC3077798 · DOI
  76. [77]Curotto de Lafaille MA Lafaille JJ: Natural and adaptive foxp3 + regulatory T cells: more of the same or a division of labor? Immunity. 2009; 30(5): 626– 35. 10.1016/j.immuni.2009.05.002 19464985 · DOI
  77. [78]Zheng Y Josefowicz S Chaudhry A: Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature. 2010; 463(7282): 808– 12. 10.1038/nature08750 20072126 PMC2884187 · DOI
  78. [79]Sumpter TL Payne KK Wilkes DS: Regulation of the NFAT pathway discriminates CD4 +CD25 + regulatory T cells from CD4 +CD25 - helper T cells. J Leukoc Biol. 2008; 83(3): 708– 17. 10.1189/jlb.0507321 18032693 · DOI
  79. [80]Bopp T Palmetshofer A Serfling E: NFATc2 and NFATc3 transcription factors play a crucial role in suppression of CD4 + T lymphocytes by CD4 + CD25 + regulatory T cells. J Exp Med. 2005; 201(2): 181– 7. 10.1084/jem.20041538 15657288 PMC2212786 · DOI
  80. [81]Karwot R Übel C Bopp T: Increased immunosuppressive function of CD4 +CD25 +Foxp3 +GITR+ T regulatory cells from NFATc2 (-/-) mice controls allergen-induced experimental asthma. Immunobiology. 2012; 217(9): 905– 11. 10.1016/j.imbio.2012.01.004 22317750 · DOI
  81. [82]Vaeth M Bäuerlein CA Pusch T: Selective NFAT targeting in T cells ameliorates GvHD while maintaining antitumor activity. Proc Natl Acad Sci U S A. 2015; 112(4): 1125– 30. 10.1073/pnas.1409290112 25583478 PMC4313840 · DOI
  82. [83]Bettelli E Dastrange M Oukka M: Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to repress cytokine gene expression and effector functions of T helper cells. Proc Natl Acad Sci U S A. 2005; 102(14): 5138– 43. 10.1073/pnas.0501675102 15790681 PMC555574 · DOI
  83. [84]Vaeth M Gogishvili T Bopp T: Regulatory T cells facilitate the nuclear accumulation of inducible cAMP early repressor (ICER) and suppress nuclear factor of activated T cell c1 (NFATc1). Proc Natl Acad Sci U S A. 2011; 108(6): 2480– 5. 10.1073/pnas.1009463108 21262800 PMC3038697 · DOI
  84. [85]Bodor J Bopp T Vaeth M: Cyclic AMP underpins suppression by regulatory T cells. Eur J Immunol. 2012; 42(6): 1375– 84. 10.1002/eji.201141578 22678893 · DOI
  85. [86]Bodor J Habener JF: Role of transcriptional repressor ICER in cyclic AMP-mediated attenuation of cytokine gene expression in human thymocytes. J Biol Chem. 1998; 273(16): 9544– 51. 10.1074/jbc.273.16.9544 9545284 · DOI
  86. [87]Torgerson TR Genin A Chen C: FOXP3 inhibits activation-induced NFAT2 expression in T cells thereby limiting effector cytokine expression. J Immunol. 2009; 183(2): 907– 15. 10.4049/jimmunol.0800216 19564342 PMC2778477 · DOI
  87. [88]Linterman MA Pierson W Lee SK: Foxp3 + follicular regulatory T cells control the germinal center response. Nat Med. 2011; 17(8): 975– 82. 10.1038/nm.2425 21785433 PMC3182542 · DOI · Paper page
  88. [89]Wing JB Ise W Kurosaki T: Regulatory T cells control antigen-specific expansion of Tfh cell number and humoral immune responses via the coreceptor CTLA-4. Immunity. 2014; 41(6): 1013– 25. 10.1016/j.immuni.2014.12.006 25526312 · DOI
  89. [90]Panduro M Benoist C Mathis D: Tissue Tregs. Annu Rev Immunol. 2016; 34: 609– 33. 10.1146/annurev-immunol-032712-095948 27168246 PMC4942112 · DOI · Paper page
  90. [91]Heissmeyer V Macián F Im SH: Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins. Nat Immunol. 2004; 5(3): 255– 65. 10.1038/ni1047 14973438 · DOI
  91. [92]Heissmeyer V Macián F Varma R: A molecular dissection of lymphocyte unresponsiveness induced by sustained calcium signalling. Novartis Found Symp. 2005; 267: 165– 74; discussion 174–9. 15999806
  92. [95]Schietinger A Greenberg PD: Tolerance and exhaustion: defining mechanisms of T cell dysfunction. Trends Immunol. 2014; 35(2): 51– 60. 10.1016/j.it.2013.10.001 24210163 PMC3946600 · DOI
  93. [96]Ames RY Ting LM Gendlina I: The Transcription Factor NFAT1 Participates in the Induction of CD4 + T Cell Functional Exhaustion during Plasmodium yoelii Infection. Infect Immun. 2017; 85(9): pii: e00364-17. 10.1128/IAI.00364-17 28630062 PMC5563568 · DOI · Paper page
  94. [97]Soto-Nieves N Puga I Abe BT: Transcriptional complexes formed by NFAT dimers regulate the induction of T cell tolerance. J Exp Med. 2009; 206(4): 867– 76. 10.1084/jem.20082731 19307325 PMC2715123 F1000 Recommendation · DOI · Paper page
  95. [98]Macián F García-Cózar F Im SH: Transcriptional mechanisms underlying lymphocyte tolerance. Cell. 2002; 109(6): 719– 31. 10.1016/S0092-8674(02)00767-5 12086671 F1000 Recommendation · DOI
  96. [99]Macián F García-Rodríguez C Rao A: Gene expression elicited by NFAT in the presence or absence of cooperative recruitment of Fos and Jun. EMBO J. 2000; 19(17): 4783– 95. 10.1093/emboj/19.17.4783 10970869 PMC302068 · DOI
  97. [100]Puga I Rao A Macian F: Targeted cleavage of signaling proteins by caspase 3 inhibits T cell receptor signaling in anergic T cells. Immunity. 2008; 29(2): 193– 204. 10.1016/j.immuni.2008.06.010 18701083 PMC2630799 · DOI
  98. [101]Oukka M Ho IC de la Brousse FC: The transcription factor NFAT4 is involved in the generation and survival of T cells. Immunity. 1998; 9(3): 295– 304. 10.1016/S1074-7613(00)80612-3 9768749 · DOI
  99. [102]Ranger AM Oukka M Rengarajan J: Inhibitory function of two NFAT family members in lymphoid homeostasis and Th2 development. Immunity. 1998; 9(5): 627– 35. 10.1016/S1074-7613(00)80660-3 9846484 · DOI
  100. [103]Rengarajan J Mittelstadt PR Mages HW: Sequential involvement of NFAT and Egr transcription factors in FasL regulation. Immunity. 2000; 12(3): 293– 300. 10.1016/S1074-7613(00)80182-X 10755616 · DOI
  101. [104]Xanthoudakis S Viola JP Shaw KT: An enhanced immune response in mice lacking the transcription factor NFAT1. Science. 1996; 272(5263): 892– 5. 10.1126/science.272.5263.892 8629027 · DOI
  102. [105]Hodge MR Ranger AM Charles de la Brousse F: Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice. Immunity. 1996; 4(4): 397– 405. 10.1016/S1074-7613(00)80253-8 8612134 · DOI
  103. [106]Abe BT Shin DS Mocholi E: NFAT1 supports tumor-induced anergy of CD4 (+) T cells. Cancer Res. 2012; 72(18): 4642– 51. 10.1158/0008-5472.CAN-11-3775 22865456 PMC3445721 · DOI
  104. [107]Mak TW Grusdat M Duncan GS: Glutathione Primes T Cell Metabolism for Inflammation. Immunity. 2017; 46(4): 675– 89. 10.1016/j.immuni.2017.03.019 28423341 · DOI · Paper page
  105. [109]Sena LA Li S Jairaman A: Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity. 2013; 38(2): 225– 36. 10.1016/j.immuni.2012.10.020 23415911 PMC3582741 · DOI · Paper page
  106. [110]Klein-Hessling S Muhammad K Klein M: NFATc1 controls the cytotoxicity of CD8 + T cells. Nat Commun. 2017; 8(1): 511. 10.1038/s41467-017-00612-6 28894104 PMC5593830 · DOI
  107. [111]Buck MD O'Sullivan D Pearce EL: T cell metabolism drives immunity. J Exp Med. 2015; 212(9): 1345– 60. 10.1084/jem.20151159 26261266 PMC4548052 · DOI
  108. [112]Pearce EL Poffenberger MC Chang CH: Fueling immunity: insights into metabolism and lymphocyte function. Science. 2013; 342(6155): 1242454. 10.1126/science.1242454 24115444 PMC4486656 · DOI · Paper page
  109. [113]Newton R Priyadharshini B Turka LA: Immunometabolism of regulatory T cells. Nat Immunol. 2016; 17(6): 618– 25. 10.1038/ni.3466 27196520 PMC5006394 · DOI
  110. [114]Buck MD Sowell RT Kaech SM: Metabolic Instruction of Immunity. Cell. 2017; 169(4): 570– 86. 10.1016/j.cell.2017.04.004 28475890 PMC5648021 · DOI
  111. [115]Walczak-Drzewiecka A Ratajewski M Wagner W: HIF-1alpha is up-regulated in activated mast cells by a process that involves calcineurin and NFAT. J Immunol. 2008; 181(3): 1665– 72. 10.4049/jimmunol.181.3.1665 18641302 · DOI
  112. [116]Köenig A Linhart T Schlengemann K: NFAT-induced histone acetylation relay switch promotes c-Myc-dependent growth in pancreatic cancer cells. Gastroenterology. 2010; 138(3): 1189– 99.e1-2. 10.1053/j.gastro.2009.10.045 19900447 PMC2895621 · DOI
  113. [117]Singh G Singh SK König A: Sequential activation of NFAT and c-Myc transcription factors mediates the TGF-beta switch from a suppressor to a promoter of cancer cell proliferation. J Biol Chem. 2010; 285(35): 27241– 50. 10.1074/jbc.M110.100438 20516082 PMC2930723 · DOI
  114. [118]Mognol GP de Araujo-Souza PS Robbs BK: Transcriptional regulation of the c-Myc promoter by NFAT1 involves negative and positive NFAT-responsive elements. Cell Cycle. 2012; 11(5): 1014– 28. 10.4161/cc.11.5.19518 22333584 · DOI
  115. [119]Brand A Singer K Koehl GE: LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells. Cell Metab. 2016; 24(5): 657– 71. 10.1016/j.cmet.2016.08.011 27641098 · DOI · Paper page
  116. [120]O'Neill LA Kishton RJ Rathmell J: A guide to immunometabolism for immunologists. Nat Rev Immunol. 2016; 16(9): 553– 65. 10.1038/nri.2016.70 27396447 PMC5001910 · DOI · Paper page
  117. [121]Robbs BK Cruz AL Werneck MB: Dual roles for NFAT transcription factor genes as oncogenes and tumor suppressors. Mol Cell Biol. 2008; 28(23): 7168– 81. 10.1128/MCB.00256-08 18809576 PMC2593389 · DOI
  118. [122]Ranger AM Grusby MJ Hodge MR: The transcription factor NF-ATc is essential for cardiac valve formation. Nature. 1998; 392(6672): 186– 90. 10.1038/32426 9515964 · DOI · Paper page
  119. [123]Peng SL Gerth AJ Ranger AM: NFATc1 and NFATc2 together control both T and B cell activation and differentiation. Immunity. 2001; 14(1): 13– 20. 10.1016/S1074-7613(01)00085-1 11163226 · DOI

Cited by

Sorted by citations

Authors
Vaeth, M., & Feske, S.
Affiliations
New York University (US)
Corresponding author
Feske, Stefan
ORCID
Venue
F1000Research
Publisher
F1000 Research Ltd
Published
2018-03-02
Volume
7
Pages
260
ISSN
2046-1402 (ISSN-L)
DOI
10.12688/f1000research.13426.1
PMC
PMC5840618
OpenAlex
W2791358733
Cited by
191
References
4
Citations by year
2026: 19 · 2025: 16 · 2024: 20 · 2023: 32 · 2022: 27 · 2021: 33 · 2020: 28 · 2019: 12 · 2018: 3
FWCI
1.86
Type
journal article
Language
en
Open access
Licence
Locations
  • F1000Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health (AI130143, AI097302)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
NFAT, calcineurin, T cells, humoral immune response, immune tolerance, immunometabolism, transcription factors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review