FOXP3 and scurfy: how it all began (original) (raw)

• Russell, W. L. X-ray induced mutations in mice. Cold Spring Harb. Symp. Quant. Biol. 16, 327–336 (1951).
  CAS PubMed Google Scholar
• Russell, W. L., Russell, L. B. & Kelly, E. M. Radiation dose rate and mutation frequency. Science 128, 1546–1550 (1958).
  CAS PubMed Google Scholar
• Russell, W. L., Russell, L. B. & Gower, J. S. Exceptional inheritance of a sex-linked gene in the mouse explained on the basis that the X/O sex-chromosome constitution is female. Proc. Natl Acad. Sci. USA 45, 554–560 (1959).
  CAS PubMed PubMed Central Google Scholar
• Godfrey, V., Wilkinson, J. E., Rinchik, E. M. & Russell, L. B. Fatal lymphoreticular disease in the scurfy (sf) mouse requires T cells that mature in a sf thymic environment: Potential model for thymic education. Proc. Natl Acad. Sci, USA 88, 5528–5532 (1991).
  CAS PubMed PubMed Central Google Scholar
• Godfrey, V., Wilkinson, J. E. & Russell, L. B. X-linked lymphoreticular disease in the scrufy (sf) mutant mouse. Am. J. Pathol. 138, 1379–1387 (1991).
  CAS PubMed PubMed Central Google Scholar
• Godfrey, V., Rouse, B. T. & Wilkinson, J. E. Transplantation of T cell-mediated lymphoreticular disease from the scurfy (sf) mouse. Am. J. Pathol. 145, 281–286 (1994).
  CAS PubMed PubMed Central Google Scholar
• Kanangat, S. et al. Disease in the scurfy (sf) mouse is associated with overexpression of cytokine genes. Eur. J. Immunol. 26, 161–165 (1996).
  CAS PubMed Google Scholar
• Zahorsky-Reeves, J. L. & Wilkinson, J. E. The murine mutations scurfy (sf) results in an antigen-dependent lymphoproliferative disease with altered T cell sensitivity. Eur. J. Immunol. 31, 196–204 (2001).
  CAS PubMed Google Scholar
• Blair, P. J. et al. CD4+CD8− T cells are the effector cells in disease pathogenesis in the scurfy (sf) mouse. J. Immunol. 153, 3764–3774 (1994).
  CAS PubMed Google Scholar
• Tivol, E. A. et al. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3, 541–547 (1995).
  CAS PubMed Google Scholar
• Waterhouse, P. et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 270, 985–988 (1995).
  CAS PubMed Google Scholar
• Brunkow, M. E. et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nature Genet. 27, 68–73 (2001).
  CAS PubMed Google Scholar
• Khattri, R. et al. The amount of scurfin protein determines peripheral T cell number and responsiveness. J. Immunol. 167, 6312–6320 (2001).
  CAS PubMed Google Scholar
• Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M. & Toda, M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155, 1151–1164 (1995).
  CAS PubMed Google Scholar
• Shevach, E. M. Regulatory T cells in autoimmunity. Annu. Rev. Immunol. 18, 423–449 (2000).
  CAS PubMed Google Scholar
• Thornton, A. M. & Shevach, E. M. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 188, 287–296 (1998).
  CAS PubMed PubMed Central Google Scholar
• Takahashi, T. et al. 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 (1998).
  CAS PubMed Google Scholar
• Khattri, R., Cox, T., Yasayko, S. A. & Ramsdell, F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nature Immunol. 4, 337–342 (2003).
  CAS Google Scholar
• Hori, S., Nomura, T. & Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057–1061 (2003).
  CAS PubMed Google Scholar
• Fontenot, J. D., Gavin, M. A. & Rudensky, A. Y. FoxP3 programs the development and function of CD4+CD25+ regulatory T cells. Nature Immunol. 4, 330–336 (2003).
  CAS Google Scholar
• Powell, B. R., Buist, N. & Stenzel, P. An X-linked syndrome of diarrhea, polyendocrinopathy, and fatal infection in infancy. J. Pediatr. 100, 731–737 (1982).
  CAS PubMed Google Scholar
• Bennett, C. L. et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutation of FOXP3. Nature Genet. 27, 20–21 (2001).
  CAS PubMed Google Scholar
• Wildin, R. S. et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nature Genet. 27, 18–20 (2001).
  CAS PubMed Google Scholar
• Fontenot, J. D. et al. Regulatory T cell lineage specification by the forkhead transcription factor Foxp3. Immunity 22, 329–341 (2005).
  CAS PubMed Google Scholar
• Lahl, K. et al. Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J. Exp. Med. 204, 57–63 (2007).
  CAS PubMed PubMed Central Google Scholar
• Kim, J. M., Rasmussen, J. P. & Rudensky, A. Y. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nature Immunol. 8, 191–197 (2007).
  CAS Google Scholar
• Bluestone, J. A. & Abbas, A. K. Natural versus adapted regulatory T cells. Nature Rev. Immunol. 3, 253–257 (2003).
  CAS Google Scholar
• Yadav, M., Stephan, S. & Bluestone, J. A. Peripherally induced Tregs - role in immune homeostasis and autoimmunity. Front. Immunol. 4, 232 (2013).
  CAS PubMed PubMed Central Google Scholar
• Lathrop, S. K., Santacruz, N. A., Pham, D., Luo, J. & Hsieh, C. S. Antigen-specific peripheral shaping of the natural regulatory T cell population. J. Exp. Med. 205, 3105–3117 (2008).
  CAS PubMed PubMed Central Google Scholar
• Kuczma, M. et al. TCR repertoire and Foxp3 expression define functionally distinct subsets of CD4+ regulatory T cells. J. Immunol. 183, 3118–3129 (2009).
  CAS PubMed Google Scholar
• Rubtsov, Y. P. et al. Stability of the regulatory T cell lineage in vivo. Science 329, 1667–1671 (2010).
  CAS PubMed PubMed Central Google Scholar
• Miyao, T. et al. Plasticity of Foxp3+ T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells. Immunity 36, 262–275 (2012).
  CAS PubMed Google Scholar
• Sakaguchi, S., Vignali, D. A., Rudensky, A. Y., Niec, R. E. & Waldmann, H. The plasticity and stability of regulatory T cells. Nature Rev. Immunol. 13, 461–467 (2013).
  CAS Google Scholar
• Schubert, L. A., Jeffery, E. W., Zhang, Y., Ramsdell, F. & Ziegler, S. F. Scurfin (FOXP3) acts as a repressor of transcription and regulates T cell activation. J. Biol. Chem. 276, 37672–37679 (2001).
  CAS PubMed Google Scholar
• Lopes, J. E. et al. Analysis of FOXP3 reveals multiple domains required for its function as a transcriptional repressor. J. Immunol. 177, 3133–3142 (2006).
  CAS PubMed Google Scholar
• Li, B. et al. FOXP3 is a homo-oligomer and a component of a supramolecular regulatory complex disabled in the human XLAAD/IPEX auoimmune disease. Int. Immunol. 19, 825–835 (2007).
  CAS PubMed Google Scholar
• Li, B. et al. FOXP3 interactions with histone acetyltransferase and class II histone deacetylases are required for repression. Proc. Natl Acad. Sci. USA 104, 4571–4576 (2007).
  CAS PubMed PubMed Central Google Scholar
• Pan, F. et al. Eos mediates Foxp3-dependent gene silencing in CD4+ regulatory T cells. Science 325, 1142–1146 (2009).
  CAS PubMed PubMed Central Google Scholar
• Du, J., Huang, C., Zhou, B. & Ziegler, S. F. Isoform-specific inhibition of RORα-mediated transcriptional activation by human FOXP3. J. Immunol. 180, 4785–4792 (2008).
  CAS PubMed Google Scholar
• Zhou, L. et al. TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function. Nature 453, 236–240 (2008).
  CAS PubMed PubMed Central Google Scholar
• Walker, M. R. et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25− T cells. J. Clin. Invest. 112, 1437–1443 (2003).
  CAS PubMed Google Scholar
• Bandukwala, H. S. et al. Structure of a domain-swapped FOXP3 dimer on DNA and its function in regulatory T cells. Immunity 34, 479–491 (2011).
  CAS PubMed PubMed Central Google Scholar
• Ono, M. et al. Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1. Nature 446, 685–689 (2007).
  CAS PubMed Google Scholar
• Bettelli, E., Dastrange, M. & Oukka, M. Foxp3 interacts with nuclear factor of activated T cells and NF-κB to repress cytokine gene expression and effector functions of T helper cells. Proc. Natl Acad. Sci. USA 102, 5138–5143 (2005).
  CAS PubMed PubMed Central Google Scholar
• Wu, Y. et al. FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell 126, 375–387 (2006).
  CAS PubMed Google Scholar
• Rudra, D. et al. Transcription factor Foxp3 and its protein partners form a complex regulatory network. Nature Immunol. 13, 1010–1019 (2012).
  CAS Google Scholar
• Marson, A. et al. Foxp3 occupancy and regulation of key target genes during T-cell stimulation. Nature 445, 931–935 (2007).
  CAS PubMed PubMed Central Google Scholar
• Zheng, Y. et al. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature 445, 936–940 (2007).
  CAS PubMed Google Scholar
• Mantel, P. Y. et al. Molecular mechanisms underlying FOXP3 induction in human T cells. J. Immunol. 176, 3593–3602 (2006).
  CAS PubMed Google Scholar
• Zorn, E. et al. 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 108, 1571–1579 (2006).
  CAS PubMed PubMed Central Google Scholar
• Kim, H. P. & Leonard, W. J. CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation. J. Exp. Med. 204, 1543–1551 (2007).
  CAS PubMed PubMed Central Google Scholar
• Baron, U. et al. DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3+ conventional T cells. Eur. J. Immunol. 37, 2378–2389 (2007).
  CAS PubMed Google Scholar
• Floess, S. et al. Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol. 5, e38 (2007).
  PubMed PubMed Central Google Scholar
• Huehn, J., Polansky, J. K. & Hamann, A. Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage? Nature Rev. Immunol. 9, 83–89 (2009).
  CAS Google Scholar
• Polansky, J. K. et al. DNA methylation controls Foxp3 gene expression. Eur. J. Immunol. 38, 1654–1663 (2008).
  CAS PubMed Google Scholar
• Ruan, Q. et al. Development of Foxp3+ regulatory T cells is driven by the c-Rel enhanceosome. Immunity 31, 932–940 (2009).
  CAS PubMed PubMed Central Google Scholar
• Long, M., Park, S.-G., Strickland, I., Hayden, M. S. & Ghosh, S. Nuclear factor-κB modeulates regulatory T cell development by directly regulating expression of Foxp3 transcription factor. Immunity 31, 921–931 (2009).
  CAS PubMed Google Scholar
• Deenick, E. K. et al. c-Rel but not NF-κB1 is important for T regulatory cell development. Eur. J. Immunol. 40, 677–681 (2010).
  CAS PubMed Google Scholar
• Visekruna, A. et al. c-Rel is crucial for the induction of Foxp3+ regulatory CD4+ T cells but not TH17 cells. Eur. J. Immunol. 40, 671–676 (2010).
  CAS PubMed Google Scholar
• Isomura, I. et al. c-Rel is required for the development of thymic Foxp3+ CD4 regulatory T cells. J. Exp. Med. 206, 3001–3014 (2009).
  CAS PubMed PubMed Central Google Scholar
• Zheng, Y. et al. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 463, 808–812 (2010).
  CAS PubMed PubMed Central Google Scholar
• Tone, Y. et al. Smad3 and NFAT cooperate to induce Foxp3 expression through it enhancer. Nature Immunol. 9, 194–202 (2008).
  CAS Google Scholar
• Kitoh, A. et al. Indispensable role of gthe Runx1-Cbfβ transcription complex for _in vivo_-suppressive function of FoxP3+ regulatory T cells. Immunity 31, 609–620 (2009).
  CAS PubMed Google Scholar
• Josefowicz, S. Z. et al. Extrathymically generated regulatory T cells control mucosal TH2 inflammation. Nature 482, 395–399 (2012).
  CAS PubMed PubMed Central Google Scholar
• Samstein, R. M., Josefowicz, S. Z., Arvey, A., Treuting, P. M. & Rudensky, A. Y. Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict. Cell 150, 29–38 (2012).
  CAS PubMed PubMed Central Google Scholar
• Walker, M. R., Carson, B. D., Nepom, G. T., Ziegler, S. F. & Buckner, J. H. De novo generation of antigen-specific CD4+CD25+ regulatory T cells from human CD4+CD25− cells. Proc. Natl Acad. Sci. USA 102, 4103–4108 (2005).
  CAS PubMed PubMed Central Google Scholar
• Gavin, M. A. et al. Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development. Proc. Natl Acad. Sci. USA 103, 6659–6664 (2006).
  CAS PubMed PubMed Central Google Scholar
• Allan, S. E. et al. Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int. Immunol. 19, 345–354 (2007).
  CAS PubMed Google Scholar
• Allan, S. E. et al. The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs. J. Clin. Invest. 115, 3276–3284 (2005).
  CAS PubMed PubMed Central Google Scholar
• 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 119, 203–211 (2006).
  CAS PubMed PubMed Central Google Scholar
• Huang, C. et al. Cutting Edge: a novel, human-specific interacting protein couples FOXP3 to a chromatin-remodeling complex that contains KAP1/TRIM28. J. Immunol. 190, 4470–4473 (2013).
  CAS PubMed Google Scholar
• Chatila, T. A. et al. JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J. Clin. Invest. 106, R75–R81 (2000).
  CAS PubMed PubMed Central Google Scholar
• Chen, W. et al. Conversion of peripheral CD4+CD25− T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor FoxP3. J. Exp. Med. 198, 1875–1886 (2003).
  CAS PubMed PubMed Central Google Scholar
• Bacchetta, R. et al. Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J. Clin. Invest. 116, 1713–1722 (2006).
  CAS PubMed PubMed Central Google Scholar
• Hill, J. A. et al. Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity 27, 786–800 (2007).
  CAS PubMed Google Scholar
• Gavin, M. A. et al. Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445, 771–775 (2007).
  CAS PubMed Google Scholar
• Lin, W. et al. Regulatory T cell development in the absence of functional Foxp3. Nature Immunol. 8, 359–368 (2007).
  CAS Google Scholar
• Williams, L. M. & Rudensky, A. Y. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nature Immunol. 8, 277–284 (2007).
  CAS Google Scholar
• Burchill, M. A., Yang, J., Vogtenhuber, C., Blazar, B. R. & Farrar, M. A. IL-2 receptor β-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells. J. Immunol. 178, 280–290 (2007).
  CAS PubMed Google Scholar
• Zhang, F., Meng, G. & Strober, W. Interactions among the transcription factors Runx1, RORγt and Foxp3 regulate the differentiation of interleukin 17-producing T cells. Nature Immunol. 9, 1297–1306 (2008).
  CAS Google Scholar
• Rudra, D. et al. Runx-CBFβ complexes control expression of the transcription factor Foxp3 in regulatory T cells. Nature Immunol. 10, 1170–1177 (2009).
  CAS Google Scholar
• Samstein, R. M. et al. Foxp3 exploits a pre-existent enhancer landscape for regulatory T cell lineage specification. Cell 151, 153–166 (2012).
  CAS PubMed PubMed Central Google Scholar