T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR

Proceedings of the National Academy of Sciences of the United States of America

Volumn 105, Issue 22, 2008, Pages 7797-7802

  Sauer, Stephan ^a   Bruno, Ludovica ^a   Hertweck, Arnulf ^a   Finlay, David ^b   Leleu, Marion ^a   Spivakov, Mikhail ^a   Knight, Zachary A ^c   Cobb, Bradley S ^a   Cantrell, Doreen ^b   O'Connor, Eric ^a   Shokat, Kevan M ^c   Fisher, Amanda G ^a   Merkenschlager, Matthias ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF DUNDEE   (United Kingdom)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HISTONE H3; LYSINE; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, MOUSE; HISTONE; ISOENZYME; LYMPHOCYTE ANTIGEN RECEPTOR; MICRORNA; PROTEIN KINASE; TRANSFORMING GROWTH FACTOR BETA;

5' UNTRANSLATED REGION; ANIMAL CELL; ARTICLE; CD4+ T LYMPHOCYTE; CHROMATIN; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME INHIBITION; GENE EXPRESSION PROFILING; METHYLATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN INDUCTION; SIGNAL TRANSDUCTION; THYMOCYTE; TRANSCRIPTION INITIATION SITE; ANIMAL; DRUG ANTAGONISM; DRUG EFFECT; DRUG POTENTIATION; GENETICS; IMMUNOLOGY; METABOLISM; MOUSE STRAIN; REGULATORY T LYMPHOCYTE;

MAMMALIA;

1-PHOSPHATIDYLINOSITOL 3-KINASE; 5' UNTRANSLATED REGIONS; ANIMALS; FORKHEAD TRANSCRIPTION FACTORS; HISTONES; ISOENZYMES; METHYLATION; MICE; MICE, INBRED STRAINS; MICRORNAS; PROTEIN KINASES; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTORS, ANTIGEN, T-CELL; SIGNAL TRANSDUCTION; T-LYMPHOCYTES, REGULATORY; TRANSCRIPTION INITIATION SITE; TRANSFORMING GROWTH FACTOR BETA;

EID: 45549098562     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.0800928105     Document Type: Article

References (46)

1. Fisher AG (2002) Cellular identity and lineage choice. Nat Rev Immunol 2:977-982.
2. Fontenot JD, Rudensky AY (2005) A well adapted regulatory contrivance: Regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol 6:331-337.
3. Sakaguchi S (2005) Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 6:345-352.
4. Marie JC, Letterio JJ, Gavin M, Rudensky AY (2005) TGF-β1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J Exp Med 201:1061-1067.
5. Brunkow ME, et al. (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.
6. Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057-1061.
7. Fontenot JD, Gavin MA, Rudensky AY (2003) FoxP3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 3:330-336.
8. Fontenot JD, et al. (2005) Regulatory T cell lineage specification by the forkhead transcription factor FoxP3. Immunity 22:329-341.
9. Khattri R, Cox T, Yasayko SA, Ramsdell F (2003) An essential role for scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 3:337-342.
10. Tran DQ, Ramsey H, Shevach EM (2007) Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is TGFβ dependent but does not confer a regulatory phenotype. Blood 110:2983-2990.
11. Hsieh CS, Zheng Y, Liang Y, Fontenot JD, Rudensky AY (2006) An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat Immunol 7:401-410.
12. + regulatory T cells. Immunity 27:493-504.
13. Kretschmer K, et al. (2005) Inducing and expanding regulatory T cell populations by foreign antigen. Nat Immunol 6:1219-1227.
14. Chen W, et al. (2003) Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. J Exp Med 198:1875-1886.
15. Coombes JL, et al. (2007) A functionally specialized population of mucosal CD103+DCs induces Foxp3+ regulatory T cells via a TGFβ and retinoic acid dependent mechanism. J Exp Med 204:1757-1764.
16. Sun CM, et al. (2007) Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 204:1775-1785.
17. Benson MJ, Pino-Lagos K, Rosemblatt M, Noelle RJ (2007) All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J Exp Med 204:1765-1774.
18. Gao W, et al. (2007) Contrasting effects of cyclosporine and rapamycin in de novo generation of alloantigen-specific regulatory T cells. Am J Transplant 7:1722-1732.
19. Battaglia M, Stabilini A, Roncarolo MG (2005) Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood 105:4743-4748.
20. Mantel PY, et al. (2006) Molecular mechanisms underlying FOXP3 induction in human T cells. J Immunol 176:3593-3602.
21. Kane LP, Weiss A (2003) The PI-3 kinase/Akt pathway and T cell activation: Pleiotropic pathways downstream of PIP3. Immunol Rev 192:7-20.
22. Camps M, et al. (2005) Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat Med 11:936-943.
23. Knight ZA, et al. (2006) A pharmacological map of the PI3K family defines a role for p110alpha in insulin signaling. Cell 125:733-747.
24. Foukas LC, et al. (2006) Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation. Nature 441:366-370.
25. Bilancio A, et al. (2006) Key role of the p110delta isoform of PI3K in B-cell antigen and IL-4 receptor signaling: Comparative analysis of genetic and pharmacologic interference with p110delta function in B cells. Blood 107:642-650.
26. Okkenhaug K, et al. (2002) Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice. Science 297:1031-1034.
27. Sabatini DM (2006) mTOR and cancer: Insights into a complex relationship. Nat Rev Cancer 6:729-734.
28. Barnett SF, et al. (2005) Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors. Biochem J 385:399-408.
29. Hagenbeek TJ, et al. (2004) The loss of PTEN allows TCR alphabeta lineage thymocytes to bypass IL-7 and Pre-TCR-mediated signaling. J Exp Med 200:883-894.
30. Hill JA, et al. (2007) Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity 27:786-800.
31. Cobb BS, et al. (2006) A role for Dicer in immune regulation. J Exp Med 203:2519-2527.
32. Inman GJ, et al. (2002) SB-431542 is a potent and specific inhibitor of TGF-β superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol Pharmacol 62:65-74.
33. Floess S, et al. (2007). Epigenetic control of the Foxp3 locus in regulatory T cells. PLoS Biol. e38.
34. Kim HP, Leonard WJ (2007) CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: A role for DNA methylation. J Exp Med 204:1543-1551.
35. Tone Y, et al. (2008) Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nat Immunol 9:194-202.
36. Spivakov M, Fisher AG (2007) Epigenetic signatures of stem-cell identity. Nat Rev Genet 8:263-271.
37. Patton DT, et al. (2006) The phosphoinositide 3-kinase p110delta is critical for the function of CD4+CD25+Foxp3+ regulatory T cells. J Immunol 177:6598-6602.
38. Haxhinasto S, Mathis D, Benoist C (2008). The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells. J Exp Med 205:565-574.
39. Walsh PT, et al. (2006) PTEN inhibits IL-2 receptor-mediated expansion of CD4+CD25+ Tregs. J Clin Invest 116:2521-2531.
40. So T, Croft M (2007) Cutting edge: OX40 inhibits TGF-β- and antigen-driven conversion of naive CD4 T cells into CD25+Foxp3+ T cells. J Immunol 179:1427-1430.
41. Lio CW, Hsieh CS (2008) A two-step process for thymic regulatory T cell development. Immunity 28:100-111.
42. Aschenbrenner K, et al. (2007). Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells. Nat Immunol 8:351 358.
43. Anderson MS, et al. (2005) The cellular mechanism of Aire control of T cell tolerance. Immunity 23:227-239.
44. Kaye J, et al. (1989) Selective development of CD4+ T cells in transgenic mice expressing a class II MHC-restricted antigen receptor. Nature 341:746-749.
45. Baxter J, et al. (2004) Histone hypomethylation is an indicator of epigenetic plasticity in quiescent lymphocytes. EMBO J 23:4462-4472.
46. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: A practical and powerful approach to multiple testing. J Roy Stat Soc B 57:289-300.