Subcellular localization of FOXP3 in human regulatory and nonregulatory T cells

European Journal of Immunology

Volumn 42, Issue 6, 2012, Pages 1627-1638

  Magg, Thomas ^a   Mannert, Joachim ^a   Ellwart, Joachim W ^b   Schmid, Irene ^a   Albert, Michael H ^a  

^a LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^b INSTITUTE OF EPIDEMIOLOGY   (Germany)

Author keywords

Activated T cell; FOXP3; Nuclear cytoplasmic shuttling; Treg cell

Indexed keywords

INTERLEUKIN 2; INTERLEUKIN 4; TRANSCRIPTION FACTOR FOXP3; TUMOR NECROSIS FACTOR ALPHA;

ARTICLE; CD4+ T LYMPHOCYTE; CELL NUCLEUS; CONTROLLED STUDY; CYTOPLASM; GENE EXPRESSION; GENETIC TRANSCRIPTION; HELA CELL; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; REGULATORY T LYMPHOCYTE; SITE DIRECTED MUTAGENESIS; T LYMPHOCYTE ACTIVATION;

CELL NUCLEUS; CELLS, CULTURED; CYTOPLASM; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; LYMPHOCYTE ACTIVATION; NUCLEAR EXPORT SIGNALS; T-LYMPHOCYTES; T-LYMPHOCYTES, REGULATORY;

EID: 84862137069     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201141838     Document Type: Article

References (49)

1. Sakaguchi, S., Yamaguchi, T., Nomura, T.andOno, M., Regulatory T cells and immune tolerance. Cell 2008. 133: 775-787.
2. Bacchetta, R., Gambineri, E.andRoncarolo, M. G., Role of regulatory T cells and FOXP3 in human diseases. J. Allergy Clin. Immunol. 2007. 120: 227-235; quiz 236-227.
3. Allan, S. E., Broady, R., Gregori, S., Himmel, M. E., Locke, N., Roncarolo, M. G., Bacchetta, R.et al., CD4 +T-regulatory cells: toward therapy for human diseases. Immunol. Rev. 2008. 223: 391-421.
4. Brusko, T. M., Putnam, A. L.andBluestone, J. A., Human regulatory T cells: role in autoimmune disease and therapeutic opportunities. Immunol. Rev. 2008. 223: 371-390.
5. Di Ianni, M., Falzetti, F., Carotti, A., Terenzi, A., Castellino, F., Bonifacio, E., Del Papa, B.et al., Tregs prevent GvHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood 2011. 117: 3921-3928.
6. Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M.andToda, M., Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 1995. 155: 1151-1164.
7. Ermann, J., Hoffmann, P., Edinger, M., Dutt, S., Blankenberg, F. G., Higgins, J. P., Negrin, R. S.et al., Only the CD62L+ subpopulation of CD4+CD25+ regulatory T cells protects from lethal acute GVHD. Blood 2005. 105: 2220-2226.
8. McHugh, R. S., Whitters, M. J., Piccirillo, C. A., Young, D. A., Shevach, E. M., Collins, M.andByrne, M. C., CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 2002. 16: 311-323.
9. Huang, C. T., Workman, C. J., Flies, D., Pan, X., Marson, A. L., Zhou, G., Hipkiss, E. L.et al., Role of LAG-3 in regulatory T cells. Immunity 2004. 21: 503-513.
10. Takahashi, T., Tagami, T., Yamazaki, S., Uede, T., Shimizu, J., Sakaguchi, N., Mak, T. W.et al., Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory Tcells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med. 2000. 192: 303-310.
11. Allan, S. E., Crome, S. Q., Crellin, N. K., Passerini, L., Steiner, T. S., Bacchetta, R., Roncarolo, M. G.et al., Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int. Immunol. 2007. 19: 345-354.
12. Triebel, F., Jitsukawa, S., Baixeras, E., Roman-Roman, S., Genevee, C., Viegas-Pequignot, E.andHercend, T., LAG-3, a novel lymphocyte activation gene closely related to CD4. J. Exp. Med. 1990. 171: 1393-1405.
13. Walunas, T. L., Lenschow, D. J., Bakker, C. Y., Linsley, P. S., Freeman, G. J., Green, J. M., Thompson, C. B.et al., CTLA-4 can function as a negative regulator of T-cell activation. Immunity 1994. 1: 405-413.
14. Seddiki, N., Santner-Nanan, B., Martinson, J., Zaunders, J., Sasson, S., Landay, A., Solomon, M.et al., Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J. Exp. Med. 2006. 203: 1693-1700.
15. Chen, J., Schmitt, A., Giannopoulos, K., Chen, B., Rojewski, M., Dohner, H., Bunjes, D.et al., Imatinib impairs the proliferation and function of CD4+CD25+ regulatory T cells in a dose-dependent manner. Int. J. Oncol. 2007. 31: 1133-1139.
16. Clark, F. J., Gregg, R., Piper, K., Dunnion, D., Freeman, L., Griffiths, M., Begum, G.et al., Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4+CD25high regulatory T cells. Blood 2004. 103: 2410-2416.
17. Lee, J. H., Wang, L. C., Lin, Y. T., Yang, Y. H., Lin, D. T.andChiang, B. L., Inverse correlation between CD4 +regulatory T-cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus. Immunology 2006. 117: 280-286.
18. Fontenot, J. D., Gavin, M. A. and Rudensky, A. Y., Foxp3 programs the development and function of CD4+CD25 +regulatory T cells. Nat. Immunol. 2003. 4: 330-336.
19. Hori, S., Nomura, T.andSakaguchi, S., Control of regulatory T-cell development by the transcription factor Foxp3. Science 2003. 299: 1057-1061.
20. Walker, M. R., Kasprowicz, D. J., Gersuk, V. H., Benard, A., Van Landeghen, M., Buckner, J. H.andZiegler, S. F., Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J. Clin. Invest. 2003. 112: 1437-1443.
21. Kaur, G., Goodall, J. C., Jarvis, L. B.andHill Gaston, J. S., Characterisation of Foxp3 splice variants in human CD4+ and CD8+ T cells-identification of Foxp3Delta7 in human regulatory T cells. Mol. Immunol. 2010. 48: 321-332.
22. Smith, E. L., Finney, H. M., Nesbitt, A. M., Ramsdell, F.andRobinson, M. K., Splice variants of human FOXP3 are functional inhibitors of human CD4+ T-cell activation. Immunology 2006. 119: 203-211.
23. Zhou, X., Bailey-Bucktrout, S. L., Jeker, L. T., Penaranda, C., Martinez-Llordella, M., Ashby, M., Nakayama, M.et al., Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat. Immunol. 2009. 10: 1000-1007.
24. Bacchetta, R., Passerini, L., Gambineri, E., Dai, M., Allan, S. E., Perroni, L., Dagna-Bricarelli, F.et al., Defective regulatory and effector T-cell functions in patients with FOXP3 mutations. J. Clin. Invest. 2006. 116: 1713-1722.
25. Moes, N., Rieux-Laucat, F., Begue, B., Verdier, J., Neven, B., Patey, N., Torgerson, T. T.et al., Reduced expression of FOXP3 and regulatory T-cell function in severe forms of early-onset autoimmune enteropathy. Gastroenterology 2010. 139: 770-778.
26. Lopes, J. E., Torgerson, T. R., Schubert, L. A., Anover, S. D., Ocheltree, E. L., Ochs, H. D.andZiegler, S. F., Analysis of FOXP3 reveals multiple domains required for its function as a transcriptional repressor. J. Immunol. 2006. 177: 3133-3142.
27. Schubert, L. A., Jeffery, E., Zhang, Y., Ramsdell, F.andZiegler, S. F., Scurfin (FOXP3) acts as a repressor of transcription and regulates T-cell activation. J. Biol. Chem. 2001. 276: 37672-37679.
28. Miyara, M., Yoshioka, Y., Kitoh, A., Shima, T., Wing, K., Niwa, A., Parizot, C.et al., Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 2009. 30: 899-911.
29. Hoffmann, P., Eder, R., Boeld, T. J., Doser, K., Piseshka, B., Andreesen, R.andEdinger, M., Only the CD45RA +subpopulation of CD4+CD25high T cells gives rise to homogeneous regulatory T-cell lines upon in vitro expansion. Blood 2006. 108: 4260-4267.
30. Magg, T., Hartrampf, S.andAlbert, M. H., Stable nonviral gene transfer into primary human T cells. Hum. Gene. Ther. 2009. 20: 989-998.
31. Nigg, E. A., Nucleocytoplasmic transport: signals, mechanisms and regulation. Nature 1997. 386: 779-787.
32. Fischer, U., Huber, J., Boelens, W. C., Mattaj, I. W.andLuhrmann, R., The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell 1995. 82: 475-483.
33. Henderson, B. R. and Eleftheriou, A., A comparison of the activity, sequence specificity, and CRM1-dependence of different nuclear export signals. Exp. Cell Res. 2000. 256: 213-224.
34. Kanwal, C., Li, H.andLim, C. S., Model system to study classical nuclear export signals. AAPS PharmSci. 2002. 4: E18.
35. Zheng, Y., Josefowicz, S. Z., Kas, A., Chu, T. T., Gavin, M. A.andRudensky, A. Y., Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature 2007. 445: 936-940.
36. Akilesh, S., Shaffer, D. J.and Roopenian, D., Customized molecular phenotyping by quantitative gene expression and pattern recognition analysis. Genome Res. 2003. 13: 1719-1727.
37. Allan, S. E., Passerini, L., Bacchetta, R., Crellin, N., Dai, M., Orban, P. C., Ziegler, S. F.et al., The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs. J. Clin. Invest. 2005. 115: 3276-3284.
38. Wang, J., Ioan-Facsinay, A., van der Voort, E. I., Huizinga, T. W.andToes, R. E., Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur. J. Immunol. 2007. 37: 129-138.
39. van Loosdregt, J., Vercoulen, Y., Guichelaar, T., Gent, Y. Y., Beekman, J. M., van Beekum, O., Brenkman, A. B.et al., Regulation of Treg functionality by acetylation-mediated Foxp3 protein stabilization. Blood 2009. 115: 965-974.
40. Chen, C., Rowell, E. A., Thomas, R. M., Hancock, W. W. and Wells, A. D., Transcriptional regulation by Foxp3 is associated with direct promoter occupancy and modulation of histone acetylation. J. Biol. Chem. 2006. 281: 36828-36834.
41. Yagi, H., Nomura, T., Nakamura, K., Yamazaki, S., Kitawaki, T., Hori, S., Maeda, M. et al., Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int. Immunol. 2004. 16: 1643-1656.
42. Allan, S. E., Alstad, A. N., Merindol, N., Crellin, N. K., Amendola, M., Bacchetta, R., Naldini, L. et al., Generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3. Mol. Ther. 2008. 16: 194-202.
43. Allan, S. E., Song-Zhao, G. X., Abraham, T., McMurchy, A. N. and Levings, M. K., Inducible reprogramming of human T cells into Treg cells by a conditionally active form of FOXP3. Eur. J. Immunol. 2008. 38: 3282-3289.
44. Calnan, D. R.andBrunet, A., The FoxO code. Oncogene 2008. 27: 2276-2288.
45. Grant, C., Oh, U., Fugo, K., Takenouchi, N., Griffith, C., Yao, K., Newhook, T. E.et al., Foxp3 represses retroviral transcription by targeting both NF-kappaB and CREB pathways. PLoS Pathog. 2006. 2: e33.
46. Zhou, L., Lopes, J. E., Chong, M. M., Ivanov, I. I., Min, R., Victora, G. D., Shen, Y.et al., TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 2008. 453: 236-240.
47. Mailer, R. K., Falk, K.andRotzschke, O., Absence of leucine zipper in the natural FOXP3Delta2Delta7 isoform does not affect dimerization but abrogates suppressive capacity. PLoS ONE 2009. 4: e6104.
48. Albert, M. H., Yu, X. Z.andMagg, T., Ethylenecarbodiimide-coupled allogeneic antigen presenting cells induce human CD4+ regulatory T cells. Clin. Immunol. 2008. 129: 381-393.
49. Astrinidis, A., Kim, J., Kelly, C. M., Olofsson, B. A., Torabi, B., Sorokina, E. M.andAzizkhan-Clifford, J., The transcription factor SP1 regulates centriole function and chromosomal stability through a functional interaction with the mammalian target of rapamycin/raptor complex. Genes Chromosomes Cancer 2010. 49: 282-297.