The dual role of the X-linked FoxP3 gene in human cancers

Molecular Oncology

Volumn 5, Issue 2, 2011, Pages 156-163

  Redpath, Margaret ^a   Xu, Bin ^a   van Kempen, Leon C ^a,b   Spatz, Alan ^a,b  

^a MCGILL UNIVERSITY   (Canada)

^b MCGILL UNIVERSITY   (Canada)

Author keywords

Fox3P; Melanoma; T lymphocyte associated antigen 4 (CTLA 4) ipilimumab

Indexed keywords

CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 ANTIBODY; IPILIMUMAB; TRANSCRIPTION FACTOR FOXP3;

CANCER IMMUNOTHERAPY; CD4+ CD25+ T LYMPHOCYTE; EPIGENETICS; GENE FUNCTION; GENE STRUCTURE; HUMAN; MALIGNANT NEOPLASTIC DISEASE; MELANOMA; PRIORITY JOURNAL; REVIEW; TUMOR GENE; TUMOR SUPPRESSOR GENE; X CHROMOSOME LINKED DISORDER;

EID: 79955479783     PISSN: 15747891     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.molonc.2011.03.001     Document Type: Review

References (110)

1. Aarts-Riemens T., Emmelot M.E., Verdonck L.F., Mutis T. Forced overexpression of either of the two common human Foxp3 isoforms can induce regulatory T cells from CD4(+)CD25(-) cells. Eur. J. Immunol. 2008, 38:1381-1390.
2. Allan S.E., Passerini L., Bacchetta R., Crellin N., Dai M., Orban P.C., Ziegler S.F., Roncarolo M.G., Levings M.K. The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs. J. Clin. Invest. 2005, 115:3276-3284.
3. Amarnath S., Dong L., Li J., Wu Y., Chen W. Endogenous TGF-beta activation by reactive oxygen species is key to Foxp3 induction in TCR-stimulated and HIV-1-infected human CD4+CD25- T cells. Retrovirology 2007, 4:57.
4. Baron U., Floess S., Wieczorek G., Baumann K., Grutzkau A., Dong J., Thiel A., Boeld T.J., Hoffmann P., Edinger M., Turbachova I., Hamann A., Olek S., Huehn J. DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3(+) conventional T cells. Eur. J. Immunol. 2007, 37:2378-2389.
5. Bennett C.L., Brunkow M.E., Ramsdell F., O'Briant K.C., Zhu Q., Fuleihan R.L., Shigeoka A.O., Ochs H.D., Chance P.F. A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA AAUGAA) leads to the IPEX syndrome. Immunogenetics 2001, 53:435-439.
6. Blache C., Adriouch S., Calbo S., Drouot L., Dulauroy S., Arnoult C., Le Corre S., Six A., Seman M., Boyer O. Cutting edge: CD4-independent development of functional FoxP3+ regulatory T cells. J. Immunol. 2009, 183:4182-4186.
7. Bruinsma M., Wils E.J., Lowenberg B., Cornelissen J.J., Braakman E. The impact of CD4(+)Foxp3(+) Treg on immunity to murine cytomegalovirus after bone marrow transplantation depends on the peripheral or thymic source of T cell regeneration. Transpl. Immunol. 2010.
8. Buckner J.H. Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat. Rev. Immunol. 2010, 10:849-859.
9. Buckner J.H., Ziegler S.F. Functional analysis of FOXP3. Ann. N. Y. Acad. Sci. 2008, 1143:151-169.
10. Burchill M.A., Yang J., Vogtenhuber C., Blazar B.R., Farrar M.A. IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells. J. Immunol. 2007, 178:280-290.
11. Carrier Y., Yuan J., Kuchroo V.K., Weiner H.L. Th3 cells in peripheral tolerance. I. Induction of Foxp3-positive regulatory T cells by Th3 cells derived from TGF-beta T cell-transgenic mice. J. Immunol. 2007, 178:179-185.
12. Chen G.Y., Chen C., Wang L., Chang X., Zheng P., Liu Y. Cutting edge: broad expression of the FoxP3 locus in epithelial cells: a caution against early interpretation of fatal inflammatory diseases following in vivo depletion of FoxP3-expressing cells. J. Immunol. 2008, 180:5163-5166.
13. Chen W., Konkel J.E. TGF-beta and 'adaptive' Foxp3(+) regulatory T cells. J. Mol. Cell Biol. 2010, 2:30-36.
14. Chen X., Hamano R., Subleski J.J., Hurwitz A.A., Howard O.M., Oppenheim J.J. Expression of costimulatory TNFR2 induces resistance of CD4+FoxP3- conventional T cells to suppression by CD4+FoxP3+ regulatory T cells. J. Immunol. 2010, 185:174-182.
15. Ebelt K., Babaryka G., Frankenberger B., Stief C.G., Eisenmenger W., Kirchner T., Schendel D.J., Noessner E. Prostate cancer lesions are surrounded by FOXP3-, PD-1+ and B7-H1+ lymphocyte clusters. Eur. J. Cancer 2009, 45:1664-1672.
16. Fantini M.C., Becker C., Monteleone G., Pallone F., Galle P.R., Neurath M.F. Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25- T cells through Foxp3 induction and down-regulation of Smad7. J. Immunol. 2004, 172:5149-5153.
17. Floess S., Freyer J., Siewert C., Baron U., Olek S., Polansky J., Schlawe K., Chang H.D., Bopp T., Schmitt E., Klein-Hessling S., Serfling E., Hamann A., Huehn J. Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol. 2007, 5:e38.
18. Fontenot J.D., Rudensky A.Y. A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat. Immunol. 2005, 6:331-337.
19. Fu S., Zhang N., Yopp A.C., Chen D., Mao M., Zhang H., Ding Y., Bromberg J.S. TGF-beta induces Foxp3+ T-regulatory cells from CD4+ CD25- precursors. Am. J. Transplant. 2004, 4:1614-1627.
20. Fujii H., Arakawa A., Kitoh A., Miyara M., Kato M., Kore-Eda S., Sakaguchi S., Miyachi Y., Tanioka M., Ono M. Perturbations of both non-regulatory and regulatory FOXP3(+) T cells in patients with malignant melanoma. Br. J. Dermatol 2010.
21. Fujimoto M., Nakano M., Terabe F., Kawahata H., Ohkawara T., Han Y., Ripley B., Serada S., Nishikawa T., Kimura A., Nomura S., Kishimoto T., Naka T. The influence of excessive IL-6 production in vivo on the development and function of Foxp3+ regulatory T cells. J. Immunol. 2011, 186:32-40.
22. Gates J.D., Clifton G.T., Benavides L.C., Sears A.K., Carmichael M.G., Hueman M.T., Holmes J.P., Jama Y.H., Mursal M., Zacharia A., Ciano K., Khoo S., Stojadinovic A., Ponniah S., Peoples G.E. Circulating regulatory T cells (CD4+CD25+FOXP3+) decrease in breast cancer patients after vaccination with a modified MHC class II HER2/neu (AE37) peptide. Vaccine 2010, 28:7476-7482.
23. Gupta S., Joshi K., Wig J.D., Arora S.K. Intratumoral FOXP3 expression in infiltrating breast carcinoma: its association with clinicopathologic parameters and angiogenesis. Acta Oncol. 2007, 46:792-797.
24. Hancock W.W., Ozkaynak E. Three distinct domains contribute to nuclear transport of murine Foxp3. PLoS One 2009, 4:e7890.
25. Hansmann L., Schmidl C., Boeld T.J., Andreesen R., Hoffmann P., Rehli M., Edinger M. Isolation of intact genomic DNA from FOXP3-sorted human regulatory T cells for epigenetic analyses. Eur. J. Immunol. 2010, 40:1510-1512.
26. Harbuz R., Lespinasse J., Boulet S., Francannet C., Creveaux I., Benkhelifa M., Jouk P.S., Lunardi J., Ray P.F. Identification of new FOXP3 mutations and prenatal diagnosis of IPEX syndrome. Prenat. Diagn. 2010, 30:1072-1078.
27. Hodi F.S., O'Day S.J., McDermott D.F., Weber R.W., Sosman J.A., Haanen J.B., Gonzalez R., Robert C., Schadendorf D., Hassel J.C., Akerley W., van den Eertwegh A.J., Lutzky J., Lorigan P., Vaubel J.M., Linette G.P., Hogg D., Ottensmeier C.H., Lebbe C., Peschel C., Quirt I., Clark J.I., Wolchok J.D., Weber J.S., Tian J., Yellin M.J., Nichol G.M., Hoos A., Urba W.J. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 2010, 363:711-723.
28. Horwitz D.A., Zheng S.G., Wang J., Gray J.D. Critical role of IL-2 and TGF-beta in generation, function and stabilization of Foxp3+CD4+ Treg. Eur. J. Immunol. 2008, 38:912-915.
29. Huber S., Stahl F.R., Schrader J., Luth S., Presser K., Carambia A., Flavell R.A., Werner S., Blessing M., Herkel J., Schramm C. Activin a promotes the TGF-beta-induced conversion of CD4+CD25- T cells into Foxp3+ induced regulatory T cells. J. Immunol. 2009, 182:4633-4640.
30. Huter E.N., Punkosdy G.A., Glass D.D., Cheng L.I., Ward J.M., Shevach E.M. TGF-beta-induced Foxp3+ regulatory T cells rescue scurfy mice. Eur. J. Immunol. 2008, 38:1814-1821.
31. Inoue N., Watanabe M., Morita M., Tomizawa R., Akamizu T., Tatsumi K., Hidaka Y., Iwatani Y. Association of functional polymorphisms related to the transcriptional level of FOXP3 with prognosis of autoimmune thyroid diseases. Clin. Exp. Immunol. 2010, 162:402-406.
32. Janson P.C., Winerdal M.E., Marits P., Thorn M., Ohlsson R., Winqvist O. FOXP3 promoter demethylation reveals the committed Treg population in humans. PLoS One 2008, 3:e1612.
33. Jung D.J., Jin D.H., Hong S.W., Kim J.E., Shin J.S., Kim D., Cho B.J., Hwang Y.I., Kang J.S., Lee W.J. Foxp3 expression in p53-dependent DNA damage responses. J. Biol. Chem. 2010, 285:7995-8002.
34. Karanikas V., Speletas M., Zamanakou M., Kalala F., Loules G., Kerenidi T., Barda A.K., Gourgoulianis K.I., Germenis A.E. Foxp3 expression in human cancer cells. J. Transl. Med. 2008, 6:19.
35. Katagiri Y., Hozumi Y., Kondo S. Knockdown of Skp2 by siRNA inhibits melanoma cell growth in vitro and in vivo. J. Dermatol. Sci. 2006, 42:215-224.
36. Katoh H., Zheng P., Liu Y. Signalling through FOXP3 as an X-linked tumor suppressor. Int. J. Biochem. Cell Biol. 2010, 42:1784-1787.
37. Kaur G., Goodall J.C., Jarvis L.B., Hill 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.
38. Kawamoto K., Pahuja A., Hering B.J., Bansal-Pakala P. Transforming growth factor beta 1 (TGF-beta1) and rapamycin synergize to effectively suppress human T cell responses via upregulation of FoxP3+ Tregs. Transpl. Immunol. 2010, 23:28-33.
39. Kim C.H. FOXP3 and its role in the immune system. Adv. Exp. Med. Biol. 2009, 665:17-29.
40. Kim H.P., Leonard W.J. CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation. J. Exp. Med. 2007, 204:1543-1551.
41. Kiniwa Y., Miyahara Y., Wang H.Y., Peng W., Peng G., Wheeler T.M., Thompson T.C., Old L.J., Wang R.F. CD8+ Foxp3+ regulatory T cells mediate immunosuppression in prostate cancer. Clin. Cancer Res. 2007, 13:6947-6958.
42. Komatsu N., Hori S. Full restoration of peripheral Foxp3+ regulatory T cell pool by radioresistant host cells in scurfy bone marrow chimeras. Proc. Natl. Acad. Sci. U S A 2007, 104:8959-8964.
43. Ladoire S., Arnould L., Mignot G., Coudert B., Rebe C., Chalmin F., Vincent J., Bruchard M., Chauffert B., Martin F., Fumoleau P., Ghiringhelli F. Presence of Foxp3 expression in tumor cells predicts better survival in HER2-overexpressing breast cancer patients treated with neoadjuvant chemotherapy. Breast Cancer Res. Treat. 2011, 125:65-72.
44. Lal G., Bromberg J.S. Epigenetic mechanisms of regulation of Foxp3 expression. Blood 2009, 114:3727-3735.
45. Lal G., Yin N., Xu J., Lin M., Schroppel S., Ding Y., Marie I., Levy D.E., Bromberg J.S. Distinct inflammatory signals have physiologically divergent effects on epigenetic regulation of foxp3 expression and treg function. Am. J. Transplant. 2011, 11:203-214.
46. Lal G., Zhang N., van der Touw W., Ding Y., Ju W., Bottinger E.P., Reid S.P., Levy D.E., Bromberg J.S. Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J. Immunol. 2009, 182:259-273.
47. Lan Y., Tang X.S., Qin J., Wu J., Qin J.M. Association of transcription factor FOXP3 gene polymorphism with genetic susceptibility to systematic lupus erythematosus in Guangxi Zhuang population. Zhonghua YiXue YiChuanXue ZaZhi 2010, 27:433-436.
48. Lee S.M., Gao B., Fang D. FoxP3 maintains Treg unresponsiveness by selectively inhibiting the promoter DNA-binding activity of AP-1. Blood 2008, 111:3599-3606.
49. Li B., Greene M.I. Special regulatory T-cell review: FOXP3 biochemistry in regulatory T cells-how diverse signals regulate suppression. Immunology 2008, 123:17-19.
50. Li R., Perez N., Karumuthil-Melethil S., Prabhakar B.S., Holterman M.J., Vasu C. Enhanced engagement of CTLA-4 induces antigen-specific CD4+CD25+Foxp3+ and CD4+CD25- TGF-beta 1+ adaptive regulatory T cells. J. Immunol. 2007, 179:5191-5203.
51. Li W., Wang L., Katoh H., Liu R., Zheng P., Liu Y. Identification of a tumor suppressor Relay between the FOXP3 and the Hippo pathways in breast and prostate cancers. Cancer Res. 2011.
52. Lin Y.C., Lee J.H., Wu A.S., Tsai C.Y., Yu H.H., Wang L.C., Yang Y.H., Chiang B.L. Association of single-nucleotide polymorphisms in FOXP3 gene with systemic lupus erythematosus susceptibility: a case-control study. Lupus 2011, 20:137-143.
53. Liu Y., Wang Y., Li W., Zheng P. Activating transcription factor 2 and c-Jun-mediated induction of FoxP3 for experimental therapy of mammary tumor in the mouse. Cancer Res. 2009, 69:5954-5960.
54. Liu Y., Zheng P. FOXP3 and breast cancer: implications for therapy and diagnosis. Pharmacogenomics 2007, 8:1485-1487.
55. Lopes J.E., Soper D.M., Ziegler S.F. Foxp3 is required throughout the life of a regulatory T cell. Sci. STKE 2007, pe36.
56. Luo X., Zhang Q., Liu V., Xia Z., Pothoven K.L., Lee C. Cutting edge: TGF-beta-induced expression of Foxp3 in T cells is mediated through inactivation of ERK. J. Immunol. 2008, 180:2757-2761.
57. Mahic M., Henjum K., Yaqub S., Bjornbeth B.A., Torgersen K.M., Tasken K., Aandahl E.M. Generation of highly suppressive adaptive CD8(+)CD25(+)FOXP3(+) regulatory T cells by continuous antigen stimulation. Eur. J. Immunol. 2008, 38:640-646.
58. Mahmoud S.M., Paish E.C., Powe D.G., Macmillan R.D., Lee A.H., Ellis I.O., Green A.R. An evaluation of the clinical significance of FOXP3(+) infiltrating cells in human breast cancer. Breast Cancer Res. Treat. 2010.
59. Maitra U., Davis S., Reilly C.M., Li L. Differential regulation of Foxp3 and IL-17 expression in CD4 T helper cells by IRAK-1. J. Immunol. 2009, 182:5763-5769.
60. Mantel P.Y., Ouaked N., Ruckert B., Karagiannidis C., Welz R., Blaser K., Schmidt-Weber C.B. Molecular mechanisms underlying FOXP3 induction in human T cells. J. Immunol. 2006, 176:3593-3602.
61. Marie J.C., Letterio J.J., Gavin M., Rudensky A.Y. TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J. Exp. Med. 2005, 201:1061-1067.
62. Merlo A., Casalini P., Carcangiu M.L., Malventano C., Triulzi T., Menard S., Tagliabue E., Balsari A. FOXP3 expression and overall survival in breast cancer. J. Clin. Oncol. 2009, 27:1746-1752.
63. Miyara M., Sakaguchi S. Human FoxP3(+)CD4(+) regulatory T cells: their knowns and unknowns. Immunol. Cell Biol 2011.
64. Miyara M., Yoshioka Y., Kitoh A., Shima T., Wing K., Niwa A., Parizot C., Taflin C., Heike T., Valeyre D., Mathian A., Nakahata T., Yamaguchi T., Nomura T., Ono M., Amoura Z., Gorochov G., Sakaguchi S. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 2009, 30:899-911.
65. Moon C., Kim S.H., Park K.S., Choi B.K., Lee H.S., Park J.B., Choi G.S., Kwan J.H., Joh J.W., Kim S.J. Use of epigenetic modification to induce FOXP3 expression in naive T cells. Transplant. Proc. 2009, 41:1848-1854.
66. Ochs H.D., Gambineri E., Torgerson T.R. IPEX, FOXP3 and regulatory T-cells: a model for autoimmunity. Immunol. Res. 2007, 38:112-121.
67. Ono M., Yaguchi H., Ohkura N., Kitabayashi I., Nagamura Y., Nomura T., Miyachi Y., Tsukada T., Sakaguchi S. Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1. Nature 2007, 446:685-689.
68. Ouaked N., Mantel P.Y., Bassin C., Burgler S., Siegmund K., Akdis C.A., Schmidt-Weber C.B. Regulation of the foxp3 gene by the Th1 cytokines: the role of IL-27-induced STAT1. J. Immunol. 2009, 182:1041-1049.
69. Owen C.J., Jennings C.E., Imrie H., Lachaux A., Bridges N.A., Cheetham T.D., Pearce S.H. Mutational analysis of the FOXP3 gene and evidence for genetic heterogeneity in the immunodysregulation, polyendocrinopathy, enteropathy syndrome. J. Clin. Endocrinol. Metab. 2003, 88:6034-6039.
70. Polansky J.K., Kretschmer K., Freyer J., Floess S., Garbe A., Baron U., Olek S., Hamann A., von Boehmer H., Huehn J. DNA methylation controls Foxp3 gene expression. Eur. J. Immunol. 2008, 38:1654-1663.
71. Polansky J.K., Schreiber L., Thelemann C., Ludwig L., Kruger M., Baumgrass R., Cording S., Floess S., Hamann A., Huehn J. Methylation matters: binding of Ets-1 to the demethylated Foxp3 gene contributes to the stabilization of Foxp3 expression in regulatory T cells. J. Mol. Med. 2010, 88:1029-1040.
72. Roncarolo M.G., Gregori S. Is FOXP3 a bona fide marker for human regulatory T cells?. Eur. J. Immunol. 2008, 38:925-927.
73. Rose A.E., Wang G., Hanniford D., Monni S., Tu T., Shapiro R.L., Berman R.S., Pavlick A.C., Pagano M., Darvishian F., Mazumdar M., Hernando E., Osman I. Clinical relevance of SKP2 alterations in metastatic melanoma. Pigment Cell Melanoma Res. 2011, 24:197-206.
74. Ruan Q., Kameswaran V., Tone Y., Li L., Liou H.C., Greene M.I., Tone M., Chen Y.H. Development of Foxp3(+) regulatory t cells is driven by the c-Rel enhanceosome. Immunity 2009, 31:932-940.
75. Rubio-Cabezas O., Minton J.A., Caswell R., Shield J.P., Deiss D., Sumnik Z., Cayssials A., Herr M., Loew A., Lewis V., Ellard S., Hattersley A.T. Clinical heterogeneity in patients with FOXP3 mutations presenting with permanent neonatal diabetes. Diabetes Care 2009, 32:111-116.
76. Sadlon T.J., Wilkinson B.G., Pederson S., Brown C.Y., Bresatz S., Gargett T., Melville E.L., Peng K., D'Andrea R.J., Glonek G.G., Goodall G.J., Zola H., Shannon M.F., Barry S.C. Genome-wide identification of human FOXP3 target genes in natural regulatory T cells. J. Immunol. 2010, 185:1071-1081.
77. Samanta A., Li B., Song X., Bembas K., Zhang G., Katsumata M., Saouaf S.J., Wang Q., Hancock W.W., Shen Y., Greene M.I. TGF-beta and IL-6 signals modulate chromatin binding and promoter occupancy by acetylated FOXP3. Proc. Natl. Acad. Sci. U S A 2008, 105:14023-14027.
78. Schneider A., Rieck M., Sanda S., Pihoker C., Greenbaum C., Buckner J.H. The effector T cells of diabetic subjects are resistant to regulation via CD4+ FOXP3+ regulatory T cells. J. Immunol. 2008, 181:7350-7355.
79. Schramm C., Huber S., Protschka M., Czochra P., Burg J., Schmitt E., Lohse A.W., Galle P.R., Blessing M. TGF-beta regulates the CD4+CD25+ T-cell pool and the expression of Foxp3 in vivo. Int. Immunol. 2004, 16:1241-1249.
80. Simonetta F., Chiali A., Cordier C., Urrutia A., Girault I., Bloquet S., Tanchot C., Bourgeois C. Increased CD127 expression on activated FOXP3+CD4+ regulatory T cells. Eur. J. Immunol. 2010, 40:2528-2538.
81. Smith E.L., Finney H.M., Nesbitt A.M., Ramsdell F., Robinson M.K. Splice variants of human FOXP3 are functional inhibitors of human CD4+ T-cell activation. Immunology 2006, 119:203-211.
82. Soligo M., Camperio C., Caristi S., Scotta C., Del Porto P., Costanzo A., Mantel P.Y., Schmidt-Weber C.B., Piccolella E. CD28 costimulation regulates FOXP3 in a RelA/NF-kappaB-dependent mechanism. Eur. J. Immunol. 2011, 41:503-513.
83. Spatz A., Borg C., Feunteun J. X-chromosome genetics and human cancer. Nat. Rev. Cancer 2004, 4:617-629.
84. Takaki H., Ichiyama K., Koga K., Chinen T., Takaesu G., Sugiyama Y., Kato S., Yoshimura A., Kobayashi T. STAT6 Inhibits TGF-beta1-mediated Foxp3 induction through direct binding to the Foxp3 promoter, which is reverted by retinoic acid receptor. J. Biol. Chem. 2008, 283:14955-14962.
85. Thornton A.M., Korty P.E., Tran D.Q., Wohlfert E.A., Murray P.E., Belkaid Y., Shevach E.M. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 2010, 184:3433-3441.
86. Torgerson T.R., Linane A., Moes N., Anover S., Mateo V., Rieux-Laucat F., Hermine O., Vijay S., Gambineri E., Cerf-Bensussan N., Fischer A., Ochs H.D., Goulet O., Ruemmele F.M. Severe food allergy as a variant of IPEX syndrome caused by a deletion in a noncoding region of the FOXP3 gene. Gastroenterology 2007, 132:1705-1717.
87. Valdman A., Jaraj S.J., Comperat E., Charlotte F., Roupret M., Pisa P., Egevad L. Distribution of Foxp3-, CD4- and CD8-positive lymphocytic cells in benign and malignant prostate tissue. APMIS 2010, 118:360-365.
88. Vang K.B., Yang J., Mahmud S.A., Burchill M.A., Vegoe A.L., Farrar M.A. IL-2, -7, and -15, but not thymic stromal lymphopoeitin, redundantly govern CD4+Foxp3+ regulatory T cell development. J. Immunol. 2008, 181:3285-3290.
89. Veldman C., Pahl A., Hertl M. Desmoglein 3-specific T regulatory 1 cells consist of two subpopulations with differential expression of the transcription factor Foxp3. Immunology 2009, 127:40-49.
90. Venuprasad K., Huang H., Harada Y., Elly C., Subramaniam M., Spelsberg T., Su J., Liu Y.C. The E3 ubiquitin ligase Itch regulates expression of transcription factor Foxp3 and airway inflammation by enhancing the function of transcription factor TIEG1. Nat. Immunol. 2008, 9:245-253.
91. Wang C., Lisanti M.P., Liao D.J. Reviewing once more the c-myc and Ras collaboration: converging at the cyclin D1-CDK4 complex and challenging basic concepts of cancer biology. Cell Cycle 2011, 10:57-67.
92. Wang D., Zhang H., Liang J., Gu Z., Zhou Q., Fan X., Hou Y., Sun L. CD4+ CD25+ but not CD4+ Foxp3+ T cells as a regulatory subset in primary biliary cirrhosis. Cell Mol. Immunol. 2010, 7:485-490.
93. Wang L., Liu R., Ribick M., Zheng P., Liu Y. FOXP3 as an X-linked tumor suppressor. Discov. Med. 2010, 10:322-328.
94. Wang L., Liu R., Li W., Chen C., Katoh H., Chen G.Y., McNally B., Lin L., Zhou P., Zuo T., Cooney K.A., Liu Y., Zheng P. Somatic single hits inactivate the X-linked tumor suppressor FOXP3 in the prostate. Cancer Cell 2009, 16:336-346.
95. Wang R., Han G., Wang J., Song L., Chen G., Xu R., Yu M., Qian J., Shen B., Li Y. The role of STAT3 in antigen-IgG inducing regulatory CD4(+)Foxp3(+)T cells. Cell Immunol. 2007, 246:103-109.
96. Wildin R.S., Freitas A. IPEX and FOXP3: clinical and research perspectives. J. Autoimmun. 2005, 25(Suppl):56-62.
97. Wu Y., Borde M., Heissmeyer V., Feuerer M., Lapan A.D., Stroud J.C., Bates D.L., Guo L., Han A., Ziegler S.F., Mathis D., Benoist C., Chen L., Rao A. FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell 2006, 126:375-387.
98. Xu L., Kitani A., Stuelten C., McGrady G., Fuss I., Strober W. Positive and negative transcriptional regulation of the Foxp3 gene is mediated by access and binding of the Smad3 protein to enhancer I. Immunity 2010, 33:313-325.
99. Yokokawa J., Cereda V., Remondo C., Gulley J.L., Arlen P.M., Schlom J., Tsang K.Y. Enhanced functionality of CD4+CD25(high)FoxP3+ regulatory T cells in the peripheral blood of patients with prostate cancer. Clin. Cancer Res. 2008, 14:1032-1040.
100. Zhang F., Meng G., Strober W. Interactions among the transcription factors Runx1, RORgammat and Foxp3 regulate the differentiation of interleukin 17-producing T cells. Nat. Immunol. 2008, 9:1297-1306.
101. Zheng Q., Xu Y., Liu Y., Zhang B., Li X., Guo F., Zhao Y. Induction of Foxp3 demethylation increases regulatory CD4+CD25+ T cells and prevents the occurrence of diabetes in mice. J. Mol. Med. 2009, 87:1191-1205.
102. Zheng S.G., Wang J.H., Stohl W., Kim K.S., Gray J.D., Horwitz D.A. TGF-beta requires CTLA-4 early after T cell activation to induce FoxP3 and generate adaptive CD4+CD25+ regulatory cells. J. Immunol. 2006, 176:3321-3329.
103. Zheng Y., Josefowicz S., Chaudhry A., Peng X.P., Forbush K., Rudensky A.Y. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 2010, 463:808-812.
104. Zhou L., Lopes J.E., Chong M.M., Ivanov, Min R., Victora G.D., Shen Y., Du J., Rubtsov Y.P., Rudensky A.Y., Ziegler S.F., Littman D.R. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 2008, 453:236-240.
105. Zhou X., Kong N., Zou H., Brand D., Li X., Liu Z., Zheng S.G. Therapeutic potential of TGF-beta-induced CD4(+) Foxp3(+) regulatory T cells in autoimmune diseases. Autoimmunity 2010.
106. Zhou Z., Song X., Li B., Greene M.I. FOXP3 and its partners: structural and biochemical insights into the regulation of FOXP3 activity. Immunol. Res. 2008, 42:19-28.
107. Ziegler S.F. FOXP3: of mice and men. Annu. Rev. Immunol. 2006, 24:209-226.
108. Zorn E., Nelson E.A., Mohseni M., Porcheray F., Kim H., Litsa D., Bellucci R., Raderschall E., Canning C., Soiffer R.J., Frank D.A., Ritz J. IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood 2006, 108:1571-1579.
109. Zuo T., Liu R., Zhang H., Chang X., Liu Y., Wang L., Zheng P. FOXP3 is a novel transcriptional repressor for the breast cancer oncogene SKP2. J. Clin. Invest. 2007, 117:3765-3773.
110. Zuo T., Wang L., Morrison C., Chang X., Zhang H., Li W., Liu Y., Wang Y., Liu X., Chan M.W., Liu J.Q., Love R., Liu C.G., Godfrey V., Shen R., Huang T.H., Yang T., Park B.K., Wang C.Y., Zheng P. FOXP3 is an X-linked breast cancer suppressor gene and an important repressor of the HER-2/ErbB2 oncogene. Cell 2007, 129:1275-1286.