Constitutive nuclear localization of NFAT in Foxp3 + regulatory T cells independent of calcineurin activity

Journal of Immunology

Volumn 188, Issue 9, 2012, Pages 4268-4277

  Li, Qiuxia ^a   Shakya, Arvind ^a   Guo, Xiaohua ^a   Zhang, Hongbo ^b   Tantin, Dean ^a   Jensen, Peter E ^a   Chen, Xinjian ^a  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^b XI'AN JIAOTONG UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

CALCINEURIN; INTERLEUKIN 2; IONOMYCIN; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3; TRANSCRIPTION FACTOR NFAT;

ANIMAL CELL; ARTICLE; CELL EXPANSION; CELL NUCLEUS; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME INHIBITION; LYMPHOCYTE PROLIFERATION; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEIN TRANSPORT; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION;

ACTIVE TRANSPORT, CELL NUCLEUS; ANIMALS; CALCINEURIN; CARCINOGENS; CELL NUCLEUS; CELL PROLIFERATION; FORKHEAD TRANSCRIPTION FACTORS; INTERLEUKIN-2; IONOMYCIN; IONOPHORES; LYMPHOCYTE ACTIVATION; MICE; MICE, TRANSGENIC; NFATC TRANSCRIPTION FACTORS; T-LYMPHOCYTES, REGULATORY; TETRADECANOYLPHORBOL ACETATE;

EID: 84860338668     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1102376     Document Type: Article

References (77)

1. Sakaguchi, S., T. Yamaguchi, T. Nomura, and M. Ono. 2008. Regulatory T cells and immune tolerance. Cell 133: 775-787. (Pubitemid 351707693)
2. Chatila, T. A., F. Blaeser, N. Ho, H. M. Lederman, C. Voulgaropoulos, C. Helms, and A. M. Bowcock. 2000. JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J. Clin. Invest. 106: R75-R81. (Pubitemid 32038594)
3. Wildin, R. S., F. Ramsdell, J. Peake, F. Faravelli, J. L. Casanova, N. Buist, E. Levy-Lahad, M. Mazzella, O. Goulet, L. Perroni, et al. 2001. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat. Genet. 27: 18-20. (Pubitemid 32044512)
4. Brunkow, M. E., E. W. Jeffery, K. A. Hjerrild, B. Paeper, L. B. Clark, S. A. Yasayko, J. E. Wilkinson, D. Galas, S. F. Ziegler, and F. Ramsdell. 2001. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 27: 68-73. (Pubitemid 32044521)
5. Bennett, C. L., J. Christie, F. Ramsdell, M. E. Brunkow, P. J. Ferguson, L. Whitesell, T. E. Kelly, F. T. Saulsbury, P. F. Chance, and H. D. Ochs. 2001. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 27: 20-21. (Pubitemid 32044513)
6. Sakaguchi, S., K. Wing, and M. Miyara. 2007. Regulatory T cells - a brief history and perspective. Eur. J. Immunol. 37(Suppl. 1): S116-S123. (Pubitemid 350131275)
7. Kim, J. M., J. P. Rasmussen, and A. Y. Rudensky. 2007. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 8: 191-197. (Pubitemid 46152650)
8. Hori, S., T. Nomura, and S. Sakaguchi. 2003. Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057-1061. (Pubitemid 36222930)
9. Rudensky, A. Y. 2011. Regulatory T cells and Foxp3. Immunol. Rev. 241: 260-268.
10. Zheng, Y., S. Z. Josefowicz, A. Kas, T. T. Chu, M. A. Gavin, and A. Y. Rudensky. 2007. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature 445: 936-940.
11. Marson, A., K. Kretschmer, G. M. Frampton, E. S. Jacobsen, J. K. Polansky, K. D. MacIsaac, S. S. Levine, E. Fraenkel, H. von Boehmer, and R. A. Young. 2007. Foxp3 occupancy and regulation of key target genes during T-cell stimulation. Nature 445: 931-935.
12. Wu, P., Y. Miura, F. Hyodoh, Y. Nishimura, T. Hatayama, S. Hatada, H. Sakaguchi, M. Kusaka, H. Katsuyama, M. Tomita, and T. Otsuki. 2006. Reduced function of CD4+25+ regulatory T cell fraction in silicosis patients. Int. J. Immunopathol. Pharmacol. 19: 357-368. (Pubitemid 44181958)
13. Bandukwala, H. S., Y. Wu, M. Feurer, Y. Chen, B. Barbosa, S. Ghosh, J. C. Stroud, C. Benoist, D. Mathis, A. Rao, and L. Chen. 2011. Structure of a domain-swapped FOXP3 dimer on DNA and its function in regulatory T cells. Immunity 34: 479-491.
14. Kitoh, A., M. Ono, Y. Naoe, N. Ohkura, T. Yamaguchi, H. Yaguchi, I. Kitabayashi, T. Tsukada, T. Nomura, Y. Miyachi, et al. 2009. Indispensable role of the Runx1-Cbfbeta transcription complex for in vivo-suppressive function of FoxP3+ regulatory T cells. Immunity 31: 609-620.
15. Ono, M., H. Yaguchi, N. Ohkura, I. Kitabayashi, Y. Nagamura, T. Nomura, Y. Miyachi, T. Tsukada, and S. Sakaguchi. 2007. Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1. Nature 446: 685-689. (Pubitemid 46606883)
16. Wu, Y., M. Borde, V. Heissmeyer, M. Feuerer, A. D. Lapan, J. C. Stroud, D. L. Bates, L. Guo, A. Han, S. F. Ziegler, et al. 2006. FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell 126: 375-387. (Pubitemid 44092960)
17. Okamura, H., C. Garcia-Rodriguez, H. Martinson, J. Qin, D. M. Virshup, and A. Rao. 2004. A conserved docking motif for CK1 binding controls the nuclear localization of NFAT1. Mol. Cell. Biol. 24: 4184-4195. (Pubitemid 41070992)
18. Gwack, Y., S. Sharma, J. Nardone, B. Tanasa, A. Iuga, S. Srikanth, H. Okamura, D. Bolton, S. Feske, P. G. Hogan, and A. Rao. 2006. A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT. Nature 441: 646-650. (Pubitemid 43927297)
19. Arron, J. R., M. M. Winslow, A. Polleri, C. P. Chang, H. Wu, X. Gao, J. R. Neilson, L. Chen, J. J. Heit, S. K. Kim, et al. 2006. NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature 441: 595-600. (Pubitemid 43927286)
20. Okamura, H., J. Aramburu, C. García-Rodríguez, J. P. Viola, A. Raghavan, M. Tahiliani, X. Zhang, J. Qin, P. G. Hogan, and A. Rao. 2000. Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity. Mol. Cell 6: 539-550.
21. Hogan, P. G., L. Chen, J. Nardone, and A. Rao. 2003. Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 17: 2205-2232. (Pubitemid 37128637)
22. Jain, J., P. G. McCaffrey, Z. Miner, T. K. Kerppola, J. N. Lambert, G. L. Verdine, T. Curran, and A. Rao. 1993. The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun. Nature 365: 352-355. (Pubitemid 23288978)
23. Loh, C., K. T. Shaw, J. Carew, J. P. Viola, C. Luo, B. A. Perrino, and A. Rao. 1996. Calcineurin binds the transcription factor NFAT1 and reversibly regulates its activity. J. Biol. Chem. 271: 10884-10891. (Pubitemid 26145827)
24. Srinivasan, M., and K. A. Frauwirth. 2007. Reciprocal NFAT1 and NFAT2 nuclear localization in CD8+ anergic T cells is regulated by suboptimal calcium signaling. J. Immunol. 179: 3734-3741.
25. Rao, A., C. Luo, and P. G. Hogan. 1997. Transcription factors of the NFAT family: regulation and function. Annu. Rev. Immunol. 15: 707-747. (Pubitemid 27169297)
26. Chen, C., E. A. Rowell, R. M. Thomas, W. W. Hancock, and A. D. Wells. 2006. Transcriptional regulation by Foxp3 is associated with direct promoter occupancy and modulation of histone acetylation. J. Biol. Chem. 281: 36828-36834. (Pubitemid 46042151)
27. Rudensky, A. Y., M. Gavin, and Y. Zheng. 2006. FOXP3 and NFAT: partners in tolerance. Cell 126: 253-256. (Pubitemid 44092973)
28. Zheng, Y., and A. Y. Rudensky. 2007. Foxp3 in control of the regulatory T cell lineage. Nat. Immunol. 8: 457-462. (Pubitemid 46605910)
29. Gavin, M. A., J. P. Rasmussen, J. D. Fontenot, V. Vasta, V. C. Manganiello, J. A. Beavo, and A. Y. Rudensky. 2007. Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445: 771-775. (Pubitemid 46279714)
30. Ruan, Q., V. Kameswaran, Y. Tone, L. Li, H. C. Liou, M. I. Greene, M. Tone, and Y. H. Chen. 2009. Development of Foxp3(+) regulatory t cells is driven by the c-Rel enhanceosome. Immunity 31: 932-940.
31. Chen, X., and P. E. Jensen. 2007. Cutting edge: primary B lymphocytes preferentially expand allogeneic FoxP3+ CD4 T cells. J. Immunol. 179: 2046-2050.
32. Lin, W., D. Haribhai, L. M. Relland, N. Truong, M. R. Carlson, C. B. Williams, and T. A. Chatila. 2007. Regulatory T cell development in the absence of functional Foxp3. Nat. Immunol. 8: 359-368. (Pubitemid 46745411)
33. Chen, L. C., J. C. Delgado, P. E. Jensen, and X. Chen. 2009. Direct expansion of human allospecific FoxP3+CD4+ regulatory T cells with allogeneic B cells for therapeutic application. J. Immunol. 183: 4094-4102.
34. Shakya, A., R. Cooksey, J. E. Cox, V. Wang, D. A. McClain, and D. Tantin. 2009. Oct1 loss of function induces a coordinate metabolic shift that opposes tumorigenicity. Nat. Cell Biol. 11: 320-327.
35. Yoshida, H., H. Nishina, H. Takimoto, L. E. Marengère, A. C. Wakeham, D. Bouchard, Y. Y. Kong, T. Ohteki, A. Shahinian, M. Bachmann, et al. 1998. The transcription factor NF-ATc1 regulates lymphocyte proliferation and Th2 cytokine production. Immunity 8: 115-124. (Pubitemid 28097829)
36. Ho, I. C., M. R. Hodge, J. W. Rooney, and L. H. Glimcher. 1996. The protooncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 85: 973-983. (Pubitemid 26231165)
37. van Rietschoten, J. G., H. H. Smits, D. van de Wetering, R. Westland, C. L. Verweij, M. T. den Hartog, and E. A. Wierenga. 2001. Silencer activity of NFATc2 in the interleukin-12 receptor beta 2 proximal promoter in human T helper cells. J. Biol. Chem. 276: 34509-34516.
38. Zhu, C., K. Rao, H. Xiong, K. Gagnidze, F. Li, C. Horvath, and S. Plevy. 2003. Activation of the murine interleukin-12 p40 promoter by functional interactions between NFAT and ICSBP. J. Biol. Chem. 278: 39372-39382. (Pubitemid 37248492)
39. Ngai, J., T. Methi, K. W. Andressen, F. O. Levy, K. M. Torgersen, T. Vang, N. Wettschureck, and K. Taskén. 2008. The heterotrimeric G-protein alpha-subunit Galphaq regulates TCR-mediated immune responses through an Lck-dependent pathway. Eur. J. Immunol. 38: 3208-3218.
40. Liu, X. K., X. Lin, and S. L. Gaffen. 2004. Crucial role for nuclear factor of activated T cells in T cell receptor-mediated regulation of human interleukin-17. J. Biol. Chem. 279: 52762-52771. (Pubitemid 39656652)
41. Agarwal, S., O. Avni, and A. Rao. 2000. Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4 enhancer in vivo. Immunity 12: 643-652.
42. Chen, L., J. N. Glover, P. G. Hogan, A. Rao, and S. C. Harrison. 1998. Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA. Nature 392: 42-48. (Pubitemid 28150581)
43. Carlsson, P., and M. Mahlapuu. 2002. Forkhead transcription factors: key players in development and metabolism. Dev. Biol. 250: 1-23.
44. Hermann-Kleiter, N., and G. Baier. 2010. NFAT pulls the strings during CD4+ T helper cell effector functions. Blood 115: 2989-2997.
45. Dienz, O., S. M. Eaton, T. J. Krahl, S. Diehl, C. Charland, J. Dodge, S. L. Swain, R. C. Budd, L. Haynes, and M. Rincon. 2007. Accumulation of NFAT mediates IL-2 expression in memory, but not naïve, CD4+ T cells. Proc. Natl. Acad. Sci. USA 104: 7175-7180. (Pubitemid 47186028)
46. Takahashi, T., Y. Kuniyasu, M. Toda, N. Sakaguchi, M. Itoh, M. Iwata, J. Shimizu, and S. Sakaguchi. 1998. Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int. Immunol. 10: 1969-1980. (Pubitemid 28566059)
47. Papiernik, M., M. L. de Moraes, C. Pontoux, F. Vasseur, and C. Pénit. 1998. Regulatory CD4 T cells: expression of IL-2R alpha chain, resistance to clonal deletion and IL-2 dependency. Int. Immunol. 10: 371-378. (Pubitemid 28182093)
48. Gavin, M. A., S. R. Clarke, E. Negrou, A. Gallegos, and A. Rudensky. 2002. Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo. Nat. Immunol. 3: 33-41. (Pubitemid 34065615)
49. Thornton, A. M., P. E. Korty, D. Q. Tran, E. A. Wohlfert, P. E. Murray, Y. Belkaid, and E. M. Shevach. 2010. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 184: 3433-3441.
50. Truneh, A., F. Albert, P. Golstein, and A. M. Schmitt-Verhulst. 1985. Early steps of lymphocyte activation bypassed by synergy between calcium ionophores and phorbol ester. Nature 313: 318-320. (Pubitemid 15151988)
51. Baier, G. 2003. The PKC gene module: molecular biosystematics to resolve its T cell functions. Immunol. Rev. 192: 64-79. (Pubitemid 36613324)
52. Manicassamy, S., M. Sadim, R. D. Ye, and Z. Sun. 2006. Differential roles of PKC-theta in the regulation of intracellular calcium concentration in primary T cells. J. Mol. Biol. 355: 347-359. (Pubitemid 41785743)
53. Kim, D. K., G. Otten, R. L. Moldwin, D. E. Dunn, G. J. Nau, and F. W. Fitch. 1986. PMA alone induces proliferation of some murine T cell clones but not others. J. Immunol. 137: 2755-2760. (Pubitemid 17177775)
54. Boulougouris, G., J. D. McLeod, Y. I. Patel, C. N. Ellwood, L. S. Walker, and D. M. Sansom. 1999. IL-2-independent activation and proliferation in human T cells induced by CD28. J. Immunol. 163: 1809-1816. (Pubitemid 29382179)
55. Hsieh, C. S., Y. Zheng, Y. Liang, J. D. Fontenot, and A. Y. Rudensky. 2006. An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat. Immunol. 7: 401-410.
56. Picca, C. C., J. Larkin, III, A. Boesteanu, M. A. Lerman, A. L. Rankin, and A. J. Caton. 2006. Role of TCR specificity in CD4+ CD25+ regulatory T-cell selection. Immunol. Rev. 212: 74-85. (Pubitemid 44116701)
57. Pacholczyk, R., J. Kern, N. Singh, M. Iwashima, P. Kraj, and L. Ignatowicz. 2007. Nonself-antigens are the cognate specificities of Foxp3+ regulatory T cells. Immunity 27: 493-504. (Pubitemid 47418672)
58. Macian, F. 2005. NFAT proteins: key regulators of T-cell development and function. Nat. Rev. Immunol. 5: 472-484. (Pubitemid 40835035)
59. Macián, F., C. López-Rodríguez, and A. Rao. 2001. Partners in transcription: NFAT and AP-1. Oncogene 20: 2476-2489. (Pubitemid 32531304)
60. Zheng, Y., A. Chaudhry, A. Kas, P. deRoos, J. M. Kim, T. T. Chu, L. Corcoran, P. Treuting, U. Klein, and A. Y. Rudensky. 2009. Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control T(H)2 responses. Nature 458: 351-356.
61. Cobb, B. S., A. Hertweck, J. Smith, E. O'Connor, D. Graf, T. Cook, S. T. Smale, S. Sakaguchi, F. J. Livesey, A. G. Fisher, and M. Merkenschlager. 2006. A role for Dicer in immune regulation. J. Exp. Med. 203: 2519-2527. (Pubitemid 44664621)
62. Kohlhaas, S., O. A. Garden, C. Scudamore, M. Turner, K. Okkenhaug, and E. Vigorito. 2009. Cutting edge: the Foxp3 target miR-155 contributes to the development of regulatory T cells. J. Immunol. 182: 2578-2582.
63. Zheng, Y., S. Josefowicz, A. Chaudhry, X. P. Peng, K. Forbush, and A. Y. Rudensky. 2010. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 463: 808-812.
64. Ferrara, J. L., J. E. Levine, P. Reddy, and E. Holler. 2009. Graft-versus-host disease. Lancet 373: 1550-1561.
65. Kasper, C., H. G. Sayer, L. O. Mügge, K. Schilling, S. Scholl, M. C. Issa, and K. Höffken. 2004. Combined standard graft-versus-host disease (GvHD) prophylaxis with mycophenolate mofetil (MMF) in allogeneic peripheral blood stem cell transplantation from unrelated donors. Bone Marrow Transplant. 33: 65-69. (Pubitemid 38159706)
66. Coenen, J. J., H. J. Koenen, E. van Rijssen, A. Kasran, L. Boon, L. B. Hilbrands, and I. Joosten. 2007. Rapamycin, not cyclosporine, permits thymic generation and peripheral preservation of CD4+ CD25+ FoxP3+ T cells. Bone Marrow Transplant. 39: 537-545. (Pubitemid 46629589)
67. Zeiser, R., V. H. Nguyen, A. Beilhack, M. Buess, S. Schulz, J. Baker, C. H. Contag, and R. S. Negrin. 2006. Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood 108: 390-399. (Pubitemid 43990654)
68. Zorn, E., H. T. Kim, S. J. Lee, B. H. Floyd, D. Litsa, S. Arumugarajah, R. Bellucci, E. P. Alyea, J. H. Antin, R. J. Soiffer, and J. Ritz. 2005. Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease. Blood 106: 2903-2911. (Pubitemid 41510772)
69. Rezvani, K., S. Mielke, M. Ahmadzadeh, Y. Kilical, B. N. Savani, J. Zeilah, K. Keyvanfar, A. Montero, N. Hensel, R. Kurlander, and A. J. Barrett. 2006. High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT. Blood 108: 1291-1297. (Pubitemid 44232027)
70. Sykes, M., M. L. Romick, K. A. Hoyles, and D. H. Sachs. 1990. In vivo administration of interleukin 2 plus T cell-depleted syngeneic marrow prevents graft-versus-host disease mortality and permits alloengraftment. J. Exp. Med. 171: 645-658. (Pubitemid 20088972)
71. Sykes, M., M. W. Harty, G. L. Szot, and D. A. Pearson. 1994. Interleukin-2 inhibits graft-versus-host disease-promoting activity of CD4+ cells while preserving CD4- and CD8-mediated graft-versus-leukemia effects. Blood 83: 2560-2569. (Pubitemid 24135848)
72. Oh-hora, M., and A. Rao. 2008. Calcium signaling in lymphocytes. Curr. Opin. Immunol. 20: 250-258.
73. Ryeom, S., R. J. Greenwald, A. H. Sharpe, and F. McKeon. 2003. The threshold pattern of calcineurin-dependent gene expression is altered by loss of the endogenous inhibitor calcipressin. Nat. Immunol. 4: 874-881. (Pubitemid 37098658)
74. Nebl, G., S. C. Meuer, and Y. Samstag. 1998. Cyclosporin A-resistant trans-activation of the IL-2 promoter requires activity of okadaic acid-sensitive serine/threonine phosphatases. J. Immunol. 161: 1803-1810. (Pubitemid 28387600)
75. Murphy, L. L., and C. C. Hughes. 2002. Endothelial cells stimulate T cell NFAT nuclear translocation in the presence of cyclosporin A: involvement of the wnt/glycogen synthase kinase-3 beta pathway. J. Immunol. 169: 3717-3725.
76. Graham, J. A., M. Fray, S. de Haseth, K. M. Lee, M. M. Lian, C. M. Chase, J. C. Madsen, J. Markmann, G. Benichou, R. B. Colvin, et al. 2010. Suppressive regulatory T cell activity is potentiated by glycogen synthase kinase 3beta inhibition. J. Biol. Chem. 285: 32852-32859.
77. Young, M. R., and B. K. Tye. 1997. Mcm2 and Mcm3 are constitutive nuclear proteins that exhibit distinct isoforms and bind chromatin during specific cell cycle stages of Saccharomyces cerevisiae. Mol. Biol. Cell 8: 1587-1601. (Pubitemid 27385578)