Foxp3

Summary

Gene Symbol: Foxp3
Description: forkhead box P3
Alias: JM2, scurfin, forkhead box protein P3, scurfy
Species: mouse
Products:     Foxp3

Top Publications

  1. Fontenot J, Gavin M, Rudensky A. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4:330-6 pubmed
    ..The lethal autoimmune syndrome observed in Foxp3-mutant scurfy mice and Foxp3-null mice results from a CD4+CD25+ regulatory T cell deficiency and not from a cell-intrinsic ..
  2. Yadav M, Louvet C, Davini D, Gardner J, Martinez Llordella M, Bailey Bucktrout S, et al. Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo. J Exp Med. 2012;209:1713-22, S1-19 pubmed
    b>Foxp3(+) CD4(+) T helper cells called regulatory T (T reg) cells play a key role in controlling reactivity to self-antigens and onset of autoimmunity...
  3. Sitrin J, Ring A, Garcia K, Benoist C, Mathis D. Regulatory T cells control NK cells in an insulitic lesion by depriving them of IL-2. J Exp Med. 2013;210:1153-65 pubmed publisher
    ..Our findings highlight the need to consider potential effects on NK cells when designing therapeutic strategies based on manipulation of IL-2 levels or targets. ..
  4. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504:451-5 pubmed publisher
    ..Regulatory T cells (Treg cells) expressing transcription factor Foxp3 have a key role in limiting inflammatory responses in the intestine...
  5. Laurence A, Amarnath S, Mariotti J, Kim Y, Foley J, Eckhaus M, et al. STAT3 transcription factor promotes instability of nTreg cells and limits generation of iTreg cells during acute murine graft-versus-host disease. Immunity. 2012;37:209-22 pubmed publisher
    ..GvHD) is a major cause of mortality in allogeneic bone marrow transplantation (BMT), for which administration of FoxP3(+) regulatory T (Treg) cells has been proposed as a therapy...
  6. Mays L, Ammon Treiber S, Mothes B, Alkhaled M, Rottenberger J, Müller Hermelink E, et al. Modified Foxp3 mRNA protects against asthma through an IL-10-dependent mechanism. J Clin Invest. 2013;123:1216-28 pubmed publisher
    ..We utilized this novel therapeutic tool to express the regulatory T cell transcription factor, FOXP3, in a time- and site-specific fashion in murine lung, in order to prevent allergic asthma in vivo...
  7. Samstein R, Arvey A, Josefowicz S, Peng X, Reynolds A, Sandstrom R, et al. Foxp3 exploits a pre-existent enhancer landscape for regulatory T cell lineage specification. Cell. 2012;151:153-66 pubmed publisher
    Regulatory T (Treg) cells, whose identity and function are defined by the transcription factor Foxp3, are indispensable for immune homeostasis...
  8. Clambey E, McNamee E, Westrich J, Glover L, Campbell E, Jedlicka P, et al. Hypoxia-inducible factor-1 alpha-dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa. Proc Natl Acad Sci U S A. 2012;109:E2784-93 pubmed publisher
    ..Surprisingly, these studies revealed selective, robust induction of FoxP3, a key transcriptional regulator for regulatory T cells (Tregs)...
  9. Gasteiger G, Hemmers S, Firth M, Le Floc h A, Huse M, Sun J, et al. IL-2-dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells. J Exp Med. 2013;210:1167-78 pubmed publisher
    ..Our results suggest that IL-2-dependent adaptive-innate lymphocyte cross talk tunes NK cell reactivity and that T reg cells restrain NK cell cytotoxicity by limiting the availability of IL-2. ..

More Information

Publications86

  1. Pierson W, Cauwe B, Policheni A, Schlenner S, Franckaert D, Berges J, et al. Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3? regulatory T cells. Nat Immunol. 2013;14:959-65 pubmed publisher
    b>Foxp3? regulatory T (Treg) cells are a crucial immunosuppressive population of CD4? T cells, yet the homeostatic processes and survival programs that maintain the Treg cell pool are poorly understood...
  2. Hansen W, Hutzler M, Abel S, Alter C, Stockmann C, Kliche S, et al. Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth. J Exp Med. 2012;209:2001-16 pubmed publisher
    Infiltration of Foxp3(+) regulatory T (T reg) cells is considered to be a critical step during tumor development and progression...
  3. van Loosdregt J, Fleskens V, Fu J, Brenkman A, Bekker C, Pals C, et al. Stabilization of the transcription factor Foxp3 by the deubiquitinase USP7 increases Treg-cell-suppressive capacity. Immunity. 2013;39:259-71 pubmed publisher
    Stable Foxp3 expression is required for the development of functional regulatory T (Treg) cells...
  4. Hall A, Beiting D, Tato C, John B, Oldenhove G, Lombana C, et al. The cytokines interleukin 27 and interferon-? promote distinct Treg cell populations required to limit infection-induced pathology. Immunity. 2012;37:511-23 pubmed publisher
    ..Thus, IFN-? and IL-27 have different roles in Treg cell biology and IL-27 is a key cytokine that promotes the development of Treg cells specialized to control Th1 cell-mediated immunity at local sites of inflammation. ..
  5. Gao Y, Nish S, Jiang R, Hou L, Licona Limón P, Weinstein J, et al. Control of T helper 2 responses by transcription factor IRF4-dependent dendritic cells. Immunity. 2013;39:722-32 pubmed publisher
    ..IRF4 is known to control Th2 cell differentiation and Th2 cell-associated suppressing function in Treg cells. Our finding suggests that IRF4 also plays a role in DCs where it controls the initiation of Th2 cell responses...
  6. Koenecke C, Lee C, Thamm K, Föhse L, Schafferus M, Mittrücker H, et al. IFN-? production by allogeneic Foxp3+ regulatory T cells is essential for preventing experimental graft-versus-host disease. J Immunol. 2012;189:2890-6 pubmed publisher
    It is emerging that CD4+Foxp3+ regulatory T (Treg) cells can produce the proinflammatory cytokine IFN-? when stimulated in a Th1 cytokine environment...
  7. Koch M, Thomas K, Perdue N, Smigiel K, Srivastava S, Campbell D. T-bet(+) Treg cells undergo abortive Th1 cell differentiation due to impaired expression of IL-12 receptor ?2. Immunity. 2012;37:501-10 pubmed publisher
    b>Foxp3(+) regulatory T (Treg) cells limit inflammatory responses and maintain immune homeostasis...
  8. Xiao X, Balasubramanian S, Liu W, Chu X, Wang H, Taparowsky E, et al. OX40 signaling favors the induction of T(H)9 cells and airway inflammation. Nat Immunol. 2012;13:981-90 pubmed publisher
    ..inhibited the production of induced regulatory T cells and the T(H)17 subset of helper T cells and diverted CD4(+)Foxp3(-) T cells to a T(H)9 phenotype...
  9. Ohkura N, Hamaguchi M, Morikawa H, Sugimura K, Tanaka A, Ito Y, et al. T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development. Immunity. 2012;37:785-99 pubmed publisher
    The transcription factor Foxp3 is essential for the development of regulatory T (Treg) cells, yet its expression is insufficient for establishing the Treg cell lineage...
  10. Ouyang W, Liao W, Luo C, Yin N, Huse M, Kim M, et al. Novel Foxo1-dependent transcriptional programs control T(reg) cell function. Nature. 2012;491:554-9 pubmed publisher
    Regulatory T (T(reg)) cells, characterized by expression of the transcription factor forkhead box P3 (Foxp3), maintain immune homeostasis by suppressing self-destructive immune responses...
  11. Zhang R, Huynh A, Whitcher G, Chang J, Maltzman J, Turka L. An obligate cell-intrinsic function for CD28 in Tregs. J Clin Invest. 2013;123:580-93 pubmed publisher
    Tregs expressing the transcription factor FOXP3 are critical for immune homeostasis...
  12. Cheng G, Yu A, Dee M, Malek T. IL-2R signaling is essential for functional maturation of regulatory T cells during thymic development. J Immunol. 2013;190:1567-75 pubmed publisher
    CD4(+) Foxp3(+) regulatory T cells (Tregs) are an independent cell lineage, and their developmental progression during thymic development depends on IL-2R signaling...
  13. Schenten D, Nish S, Yu S, Yan X, Lee H, Brodsky I, et al. Signaling through the adaptor molecule MyD88 in CD4+ T cells is required to overcome suppression by regulatory T cells. Immunity. 2014;40:78-90 pubmed publisher
    ..In addition, IL-1 was also important for the generation of functional CD4(+) memory T cells. ..
  14. Shafiani S, Dinh C, Ertelt J, Moguche A, Siddiqui I, Smigiel K, et al. Pathogen-specific Treg cells expand early during mycobacterium tuberculosis infection but are later eliminated in response to Interleukin-12. Immunity. 2013;38:1261-70 pubmed publisher
    Thymically derived Foxp3? regulatory T (Treg) cells have a propensity to recognize self-peptide:MHC complexes, but their ability to respond to epitope-defined foreign antigens during infectious challenge has not been demonstrated...
  15. Bos P, Plitas G, Rudra D, Lee S, Rudensky A. Transient regulatory T cell ablation deters oncogene-driven breast cancer and enhances radiotherapy. J Exp Med. 2013;210:2435-66 pubmed publisher
    ..role of T reg cells in murine mammary carcinogenesis using an orthotopic, polyoma middle-T antigen-driven model in Foxp3(DTR) knockin mice...
  16. Chen Z, Barbi J, Bu S, Yang H, Li Z, Gao Y, et al. The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3. Immunity. 2013;39:272-85 pubmed publisher
    ..The key Treg cell transcription factor Foxp3 is downregulated during inflammation to allow for the acquisition of effector T cell-like functions...
  17. Simpson T, Li F, Montalvo Ortiz W, Sepulveda M, Bergerhoff K, Arce F, et al. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med. 2013;210:1695-710 pubmed publisher
  18. Smith P, Howitt M, Panikov N, Michaud M, Gallini C, Bohlooly Y M, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341:569-73 pubmed publisher
    Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation...
  19. Sekiya T, Kashiwagi I, Yoshida R, Fukaya T, Morita R, Kimura A, et al. Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis. Nat Immunol. 2013;14:230-7 pubmed publisher
    ..Nr4a receptors directly activated the promoter of the gene encoding the transcription factor Foxp3, and forced activation of Nr4a receptors bypassed low-strength TCR signaling to drive the T(reg) cell ..
  20. Tai X, Erman B, Alag A, Mu J, Kimura M, Katz G, et al. Foxp3 transcription factor is proapoptotic and lethal to developing regulatory T cells unless counterbalanced by cytokine survival signals. Immunity. 2013;38:1116-28 pubmed publisher
    Immune tolerance requires regulatory T (Treg) cells to prevent autoimmune disease, with the transcription factor Foxp3 functioning as the critical regulator of Treg cell development and function...
  21. Weiss J, Bilate A, Gobert M, Ding Y, Curotto de Lafaille M, Parkhurst C, et al. Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells. J Exp Med. 2012;209:1723-42, S1 pubmed
    b>Foxp3 activity is essential for the normal function of the immune system. Two types of regulatory T (T reg) cells express Foxp3, thymus-generated natural T reg (nT reg) cells, and peripherally generated adaptive T reg (iT reg) cells...
  22. Beier U, Wang L, Han R, Akimova T, Liu Y, Hancock W. Histone deacetylases 6 and 9 and sirtuin-1 control Foxp3+ regulatory T cell function through shared and isoform-specific mechanisms. Sci Signal. 2012;5:ra45 pubmed publisher
    ..Sirt1) augments the suppressive functions of regulatory T cells (T(regs)) that contain the transcription factor Foxp3 (Forkhead box P3) and is useful in organ transplant patients or patients with autoimmune diseases...
  23. Samstein R, Josefowicz S, Arvey A, Treuting P, Rudensky A. Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict. Cell. 2012;150:29-38 pubmed publisher
    ..T (Treg) cells, whose differentiation and function are controlled by X chromosome-encoded transcription factor Foxp3, are generated in the thymus (tTreg) and extrathymically (peripheral, pTreg), and their deficiency results in ..
  24. Song X, Li B, Xiao Y, Chen C, Wang Q, Liu Y, et al. Structural and biological features of FOXP3 dimerization relevant to regulatory T cell function. Cell Rep. 2012;1:665-75 pubmed publisher
    b>FOXP3 is a key transcription factor for regulatory T cell function...
  25. Rudra D, deRoos P, Chaudhry A, Niec R, Arvey A, Samstein R, et al. Transcription factor Foxp3 and its protein partners form a complex regulatory network. Nat Immunol. 2012;13:1010-9 pubmed publisher
    The transcription factor Foxp3 is indispensible for the differentiation and function of regulatory T cells (T(reg) cells)...
  26. Delgoffe G, Woo S, Turnis M, Gravano D, Guy C, Overacre A, et al. Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis. Nature. 2013;501:252-6 pubmed publisher
    ..The transcription factor Foxp3 has a major role in the development and programming of Treg cells...
  27. Chen X, Wu X, Zhou Q, Howard O, Netea M, Oppenheim J. TNFR2 is critical for the stabilization of the CD4+Foxp3+ regulatory T. cell phenotype in the inflammatory environment. J Immunol. 2013;190:1076-84 pubmed publisher
    Several lines of evidence indicate the instability of CD4(+)Foxp3(+) regulatory T cells (Tregs). We have therefore investigated means of promoting the stability of Tregs...
  28. Cheng G, Yuan X, Tsai M, Podack E, Yu A, Malek T. IL-2 receptor signaling is essential for the development of Klrg1+ terminally differentiated T regulatory cells. J Immunol. 2012;189:1780-91 pubmed publisher
    ..These and other properties are analogous to terminally differentiated short-lived CD8(+) T effector cells. Our findings suggest that an important pathway driving Ag-activated conventional T lymphocytes also operates for Tregs. ..
  29. Rubtsov Y, Rasmussen J, Chi E, Fontenot J, Castelli L, Ye X, et al. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity. 2008;28:546-58 pubmed publisher
    ..responses through suppressor-function elaboration that is dependent upon expression of the transcription factor Foxp3. Despite a critical role for Treg cells in maintaining lympho-myeloid homeostasis, it remains unclear whether a ..
  30. Tsuji M, Komatsu N, Kawamoto S, Suzuki K, Kanagawa O, Honjo T, et al. Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches. Science. 2009;323:1488-92 pubmed publisher
    ..The nature of these T(FH) cells in Peyer's patches has been elusive. Here, we demonstrate that suppressive Foxp3+CD4+ T cells can differentiate into TFH cells in mouse Peyer's patches...
  31. Ballesteros Tato A, León B, Graf B, Moquin A, Adams P, Lund F, et al. Interleukin-2 inhibits germinal center formation by limiting T follicular helper cell differentiation. Immunity. 2012;36:847-56 pubmed publisher
    ..Our data demonstrate that IL-2 is a critical factor that regulates successful Tfh and B cell responses in vivo and regulates Tfh cell development...
  32. Kim H, Leonard W. CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation. J Exp Med. 2007;204:1543-51 pubmed
    Regulatory T cells (T reg cells) are a population of CD4+ T cells that limit immune responses. FoxP3 is a master control transcription factor for development and function of these cells, but its regulation is poorly understood...
  33. Zelenay S, Bergman M, Paiva R, Lino A, Martins A, Duarte J, et al. Cutting edge: Intrathymic differentiation of adaptive Foxp3+ regulatory T cells upon peripheral proinflammatory immunization. J Immunol. 2010;185:3829-33 pubmed publisher
    Thymocytes differentiate into CD4(+) Foxp3(+) regulatory T cells (T(R)) upon interaction between their TCR and peptide-MHC II complexes locally expressed in the thymus...
  34. Hancock W, Ozkaynak E. Three distinct domains contribute to nuclear transport of murine Foxp3. PLoS ONE. 2009;4:e7890 pubmed publisher
    b>Foxp3, a 47-kDa transcription factor, is necessary for the function of CD4+CD25+ regulatory T cells (Tregs), with an essential role in the control of self-reactive T cells and in preventing autoimmunity...
  35. Lanteri M, O Brien K, Purtha W, Cameron M, Lund J, Owen R, et al. Tregs control the development of symptomatic West Nile virus infection in humans and mice. J Clin Invest. 2009;119:3266-77 pubmed publisher
    ..Together, these results suggest that higher levels of peripheral Tregs after infection protect against severe WNV disease in immunocompetent animals and humans. ..
  36. Wei G, Abraham B, Yagi R, Jothi R, Cui K, Sharma S, et al. Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T cell types. Immunity. 2011;35:299-311 pubmed publisher
  37. Guo L, Tian J, Marinova E, Zheng B, Han S. Inhibition of clonal expansion by Foxp3 expression as a mechanism of controlled T-cell responses and autoimmune disease. Eur J Immunol. 2010;40:71-80 pubmed publisher
    The essential role of the transcription factor Foxp3 in the development and function of Treg has been well documented. The role of Foxp3 in non-Treg, however, is not fully understood...
  38. Yamazaki S, Patel M, Harper A, Bonito A, Fukuyama H, Pack M, et al. Effective expansion of alloantigen-specific Foxp3+ CD25+ CD4+ regulatory T cells by dendritic cells during the mixed leukocyte reaction. Proc Natl Acad Sci U S A. 2006;103:2758-63 pubmed
    ..Likewise, DCs and not spleen cells were effective in sustaining expression of the transcription factor Foxp3 in Tregs, but neither IL-2 nor CD80/86 was required for this effect in the cultures...
  39. Burchill M, Yang J, Vogtenhuber C, Blazar B, Farrar M. IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells. J Immunol. 2007;178:280-90 pubmed
    ..Ectopic expression of foxp3 in a subset of CD4(+) T cells rescued Treg development and prevented autoimmunity in IL-2Rbeta(-/-) mice, ..
  40. George J, Braun A, Brusko T, Joseph R, Bolisetty S, Wasserfall C, et al. Suppression by CD4+CD25+ regulatory T cells is dependent on expression of heme oxygenase-1 in antigen-presenting cells. Am J Pathol. 2008;173:154-60 pubmed publisher
    ..HO-1(-/-) mice exhibited a significantly higher proportion of Foxp3-expressing cells among total CD4(+) and CD4(+)CD25(+) cells in comparison to HO-1(+/+) mice, and HO-1(-/-) Treg ..
  41. Williams L, Rudensky A. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat Immunol. 2007;8:277-84 pubmed
    The transcription factor Foxp3 is required for the development of regulatory T cells (T(reg) cell)...
  42. Collison L, Chaturvedi V, Henderson A, Giacomin P, Guy C, Bankoti J, et al. IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol. 2010;11:1093-101 pubmed publisher
    ..We found that iT(R)35 cells did not express or require the transcription factor Foxp3, and were strongly suppressive and stable in vivo...
  43. Soper D, Kasprowicz D, Ziegler S. IL-2Rbeta links IL-2R signaling with Foxp3 expression. Eur J Immunol. 2007;37:1817-26 pubmed
    ..Recent work has demonstrated that the forkhead family member Foxp3 is a critical element in the differentiation and function of mouse CD4(+)CD25(+) regulatory T cells (Treg)...
  44. Molinero L, Yang J, Gajewski T, Abraham C, Farrar M, Alegre M. CARMA1 controls an early checkpoint in the thymic development of FoxP3+ regulatory T cells. J Immunol. 2009;182:6736-43 pubmed publisher
    ..These data suggest a modified model of nTreg development in which TCR-CBM-dependent signals are essential to commit immature thymocytes to the nTreg lineage. ..
  45. Nolting J, Daniel C, Reuter S, Stuelten C, Li P, Sucov H, et al. Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines. J Exp Med. 2009;206:2131-9 pubmed publisher
    ..Interleukin (IL)-6 strongly reduced RAR alpha expression levels such that a deficiency of the predominant RAR alpha 1 isoform leaves too little RAR alpha 2 for RA to inhibit the generation of Th17 cells in the presence of IL-6. ..
  46. Lal G, Bromberg J. Epigenetic mechanisms of regulation of Foxp3 expression. Blood. 2009;114:3727-35 pubmed publisher
    ..Mutation of the Foxp3 gene causes the scurfy phenotype in mouse and IPEX syndrome (immune dysfunction, polyendocrinopathy, enteropathy, X-linked syndrome) in ..
  47. Haribhai D, Williams J, Jia S, Nickerson D, Schmitt E, Edwards B, et al. A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity. Immunity. 2011;35:109-22 pubmed publisher
    ..We examined the functions of nTreg and iTreg cells by adoptive transfer immunotherapy of newborn Foxp3-deficient mice...
  48. Grigoriadis G, Vasanthakumar A, Banerjee A, Grumont R, Overall S, Gleeson P, et al. c-Rel controls multiple discrete steps in the thymic development of Foxp3+ CD4 regulatory T cells. PLoS ONE. 2011;6:e26851 pubmed publisher
    The development of natural Foxp3(+) CD4 regulatory T cells (nTregs) proceeds via two steps that involve the initial antigen dependent generation of CD25(+)GITR(hi)Foxp3(-)CD4(+) nTreg precursors followed by the cytokine induction of ..
  49. Brunkow M, Jeffery E, Hjerrild K, Paeper B, Clark L, Yasayko S, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet. 2001;27:68-73 pubmed
    ..In sf mice, a frameshift mutation results in a product lacking the forkhead domain. Genetic complementation demonstrates that the protein product of Foxp3, scurfin, is essential for normal immune homeostasis.
  50. Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo M. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol. 2007;8:1353-62 pubmed
    A key issue in mammalian immunology is how CD4+CD25+Foxp3+ regulatory T cells (T(reg) cells) suppress immune responses...
  51. Wollenberg I, Agua Doce A, Hernandez A, Almeida C, Oliveira V, Faro J, et al. Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells. J Immunol. 2011;187:4553-60 pubmed publisher
    ..We found that a proportion of follicular T cells, with phenotypic characteristics of T(FH) cells and expressing Foxp3, are recruited during the course of a germinal center (GC) reaction...
  52. Dang E, Barbi J, Yang H, Jinasena D, Yu H, Zheng Y, et al. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell. 2011;146:772-84 pubmed publisher
    ..Concurrently, HIF-1 attenuates T(reg) development by binding Foxp3 and targeting it for proteasomal degradation...
  53. Zahorsky Reeves J, Wilkinson J. The murine mutation scurfy (sf) results in an antigen-dependent lymphoproliferative disease with altered T cell sensitivity. Eur J Immunol. 2001;31:196-204 pubmed
    The scurfy (sf) murine mutation results in a rapidly fatal lymphoproliferative disease, causing death by 26 days. Mature CD4+ T cells which tested hyperresponsive to T cell receptor (TCR) stimulation are involved...
  54. Takahashi R, Nishimoto S, Muto G, Sekiya T, Tamiya T, Kimura A, et al. SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-{gamma} and IL-17A production. J Exp Med. 2011;208:2055-67 pubmed publisher
    ..We found that Socs1(-/-) T(reg) cells produced high levels of IFN-? and rapidly lost Foxp3 when transferred into Rag2(-/-) mice or cultured in vitro, even though the CNS2 (conserved noncoding DNA sequence ..
  55. Lee I, Wang L, Wells A, Dorf M, Ozkaynak E, Hancock W. Recruitment of Foxp3+ T regulatory cells mediating allograft tolerance depends on the CCR4 chemokine receptor. J Exp Med. 2005;201:1037-44 pubmed
    ..T cells to inflammatory sites, little is known of the mechanisms underlying a third function, migration of Foxp3(+) regulatory T (T reg) cells to sites where they maintain unresponsiveness...
  56. Baumgart M, Tompkins F, Leng J, Hesse M. Naturally occurring CD4+Foxp3+ regulatory T cells are an essential, IL-10-independent part of the immunoregulatory network in Schistosoma mansoni egg-induced inflammation. J Immunol. 2006;176:5374-87 pubmed
    ..We characterized the phenotype, distribution, and functional role of CD4(+)Foxp3(+) naturally occurring regulatory T cells (naTregs) in schistosome egg-induced inflammation...
  57. Peffault De Latour R, Dujardin H, Mishellany F, Burlen Defranoux O, Zuber J, Marques R, et al. Ontogeny, function, and peripheral homeostasis of regulatory T cells in the absence of interleukin-7. Blood. 2006;108:2300-6 pubmed
    ..We show here that the establishment of the peripheral pool of Foxp3-expressing regulatory cells is IL-7 independent, and the premature involution of the thymus in IL-7-/- mice does ..
  58. Chung H, Lee J, Kim H, Lee H, Kim S, Kwon H, et al. Foxp3 is a novel repressor of microglia activation. Glia. 2010;58:1247-56 pubmed publisher
    Forkhead transcription factor 3 (Foxp3) is critical for generating CD4(+)CD25(+) regulatory T cells. However, its role in microglia has not been identified...
  59. Murai M, Turovskaya O, Kim G, Madan R, Karp C, Cheroutre H, et al. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol. 2009;10:1178-84 pubmed publisher
    Regulatory T cells (T(reg) cells) that express the transcription factor Foxp3 suppress the activity of other cells...
  60. Chai J, Coe D, Chen D, Simpson E, Dyson J, Scott D. In vitro expansion improves in vivo regulation by CD4+CD25+ regulatory T cells. J Immunol. 2008;180:858-69 pubmed
    ..Furthermore, expanded Tregs appeared to express a reduced level of Foxp3, which could be prevented by adding TGFbeta to the culture, and they also tended to lose Foxp3 following the ..
  61. Dudda J, Perdue N, Bachtanian E, Campbell D. Foxp3+ regulatory T cells maintain immune homeostasis in the skin. J Exp Med. 2008;205:1559-65 pubmed publisher
    ..To selectively block T reg cell function in the skin, we restored the T reg cell compartment in Foxp3-deficient scurfy mice with cells whose ability to migrate to the skin was impaired because of targeted mutation of alpha-1,3-..
  62. Maynard C, Hatton R, Helms W, Oliver J, Stephensen C, Weaver C. Contrasting roles for all-trans retinoic acid in TGF-beta-mediated induction of Foxp3 and Il10 genes in developing regulatory T cells. J Exp Med. 2009;206:343-57 pubmed publisher
    ..In addition to Foxp3, T reg cell expression of suppressive cytokines, such as IL-10, is essential for peripheral tolerance, ..
  63. Wu W, Weigand L, Belkaid Y, Mendez S. Immunomodulatory effects associated with a live vaccine against Leishmania major containing CpG oligodeoxynucleotides. Eur J Immunol. 2006;36:3238-47 pubmed
    ..of dermal dendritic cells and increased IL-6 production, as well as in a reduction in the accumulation of Foxp3(+)CD4(+)CD25(+) regulatory T (T(reg)) cells that naturally occurs in the skin following Leishmania infection...
  64. Zheng S, Wang J, Wang P, Gray J, Horwitz D. IL-2 is essential for TGF-beta to convert naive CD4+CD25- cells to CD25+Foxp3+ regulatory T cells and for expansion of these cells. J Immunol. 2007;178:2018-27 pubmed
    ..Although others have reported that IL-2 can directly enhance forkhead box protein P3 (Foxp3) transcription factor expression by natural CD4(+)CD25(+) regulatory T cells, in this study, we ..
  65. Singh N, Chandler P, Seki Y, Baban B, Takezaki M, Kahler D, et al. Role of CD28 in fatal autoimmune disorder in scurfy mice. Blood. 2007;110:1199-206 pubmed
    b>Scurfy mice develop CD4 T-cell-mediated lymphoproliferative disease leading to death within 4 weeks of age...
  66. Schambach F, Schupp M, Lazar M, Reiner S. Activation of retinoic acid receptor-alpha favours regulatory T cell induction at the expense of IL-17-secreting T helper cell differentiation. Eur J Immunol. 2007;37:2396-9 pubmed
    ..acid (ATRA) leads to increased induction of CD4(+) T cells expressing the Treg specification factor forkhead box protein P3 (FoxP3) and decreased frequency of cells expressing IL-17, even in the presence of IL-6...
  67. Chen Y, Shen S, Gorentla B, Gao J, Zhong X. Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression. J Immunol. 2012;188:1698-707 pubmed publisher
    ..Treg are prone to death but hyperproliferative in vitro and in vivo, which is different from conventional CD4(+)Foxp3(-) T cells (Tcon)...
  68. Pan F, Yu H, Dang E, Barbi J, Pan X, Grosso J, et al. Eos mediates Foxp3-dependent gene silencing in CD4+ regulatory T cells. Science. 2009;325:1142-6 pubmed publisher
    ..program of Tregs and their ability to suppress pathologic immune responses depends on the transcription factor Foxp3. Despite progress in understanding mechanisms of Foxp3-dependent gene activation, the molecular mechanism of Foxp3-..
  69. Bruno L, Mazzarella L, Hoogenkamp M, Hertweck A, Cobb B, Sauer S, et al. Runx proteins regulate Foxp3 expression. J Exp Med. 2009;206:2329-37 pubmed publisher
    ..In regulatory T (T reg) cells, the signature transcription factor Foxp3 interacts with and modulates the function of several other DNA binding proteins, including Runx family members, at ..
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    Whereas TGF-beta is essential for the development of peripherally induced Foxp3(+) regulatory T cells (iTreg cells) and Th17 cells, the intracellular signaling mechanism by which TGF-beta regulates development of both cell subsets is ..
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    ..Here we found that the differentiation of proinflammatory T helper type 1 (T(H)1) cells and anti-inflammatory Foxp3(+) regulatory T cells (T(reg) cells) was reciprocally regulated by S1P(1), a receptor for the bioactive lipid ..
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    ..The CTLA-4-mediated suppression was demonstrated by the in vitro anergy induction in regulatory T cells constitutively expressing CTLA-4. These results show the dynamic mechanism of CTLA-4-mediated T cell suppression at the cSMAC. ..
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    ..mice suffered rapid and fatal autoimmunity characterized by hyperactive effector T cells and poorly suppressive Foxp3(+) Tregs...
  74. Xiao X, Kroemer A, Gao W, Ishii N, Demirci G, Li X. OX40/OX40L costimulation affects induction of Foxp3+ regulatory T cells in part by expanding memory T cells in vivo. J Immunol. 2008;181:3193-201 pubmed
    ..OX40 also inhibits the induction of Foxp3(+) regulatory T cells (Tregs) from T effector cells, but the precise mechanism of such inhibition remains unknown...
  75. Sauer S, Bruno L, Hertweck A, Finlay D, Leleu M, Spivakov M, et al. T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR. Proc Natl Acad Sci U S A. 2008;105:7797-802 pubmed publisher
    ..fate are not completely understood, we have delineated signaling events that control the de novo expression of Foxp3 in naive peripheral CD4 T cells and in thymocytes...
  76. Lio C, Dodson L, Deppong C, Hsieh C, Green J. CD28 facilitates the generation of Foxp3(-) cytokine responsive regulatory T cell precursors. J Immunol. 2010;184:6007-13 pubmed publisher
    The T cell costimulatory molecule CD28 plays an important role in the thymic generation of Foxp3(+) regulatory T cells (Tregs) essential for the maintenance of self-tolerance...
  77. Gottschalk R, Corse E, Allison J. TCR ligand density and affinity determine peripheral induction of Foxp3 in vivo. J Exp Med. 2010;207:1701-11 pubmed publisher
    T cell receptor (TCR) ligation is required for the extrathymic differentiation of forkhead box p3(+) (Foxp3(+)) regulatory T cells...