Nuclear receptor Nr4a1 modulates both regulatory T-cell (Treg) differentiation and clonal deletion

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

Volumn 109, Issue 10, 2012, Pages 3891-3896

  Fassett, Marlys S ^a   Jiang, Wenyu ^a   D'Alise, Anna Morena ^a   Mathis, Diane ^a   Benoist, Christophe ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Glycolysis; Immune tolerance; Nuclear receptor; Thymus

Indexed keywords

BIM PROTEIN; CD4 ANTIGEN; MAMMALIAN TARGET OF RAPAMYCIN; NUCLEAR RECEPTOR NUR77; PROTEIN KINASE B; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3;

ARTICLE; CD4+ T LYMPHOCYTE; CITRIC ACID CYCLE; CONTROLLED STUDY; GENE EXPRESSION PROFILING; GENETIC TRANSCRIPTION; GLYCOLYSIS; IMMUNOLOGICAL TOLERANCE; LYMPHOCYTE DIFFERENTIATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEPLETION; QUANTITATIVE ANALYSIS; REGULATORY T LYMPHOCYTE; THYMOCYTE;

ANIMALS; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; CELL DIFFERENTIATION; CELL LINEAGE; CELL NUCLEUS; GLYCOLYSIS; MEMBRANE PROTEINS; MICE; MICE, KNOCKOUT; NUCLEAR RECEPTOR SUBFAMILY 4, GROUP A, MEMBER 1; PEPTIDES; PROTO-ONCOGENE PROTEINS; T-LYMPHOCYTES, REGULATORY; THYMOCYTES; TIME FACTORS; TRANSCRIPTION FACTORS;

MUS; MUS MUSCULUS;

EID: 84857989935     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1200090109     Document Type: Article

References (49)

1. Hogquist KA, Baldwin TA, Jameson SC (2005) Central tolerance: Learning self-control in the thymus. Nat Rev Immunol 5:772-782. (Pubitemid 41400851)
2. Bouillet P, et al. (2002) BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes. Nature 415:922-926. (Pubitemid 34174755)
3. Rathmell JC, Lindsten T, Zong WX, Cinalli RM, Thompson CB (2002) Deficiency in Bak and Bax perturbs thymic selection and lymphoid homeostasis. Nat Immunol 3:932-939. (Pubitemid 35154006)
4. D'Adamio L, Clayton LK, Awad KM, Reinherz EL (1992) Negative selection of thymocytes. A novel polymerase chain reaction-based molecular analysis detects requirements for macromolecular synthesis. J Immunol 149:3550-3553.
5. Calnan BJ, Szychowski S, Chan FK, Cado D, Winoto A (1995) A role for the orphan steroid receptor Nur77 in apoptosis accompanying antigen-induced negative selection. Immunity 3:273-282.
6. Zhou T, et al. (1996) Inhibition of Nur77/Nurr1 leads to inefficient clonal deletion of self-reactive T cells. J Exp Med 183:1879-1892.
7. Lin B, et al. (2004) Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3. Cell 116:527-540. (Pubitemid 38264430)
8. Thompson J, Winoto A (2008) During negative selection, Nur77 family proteins translocate to mitochondria where they associate with Bcl-2 and expose its proapoptotic BH3 domain. J Exp Med 205:1029-1036. (Pubitemid 351679679)
9. Wang A, Rud J, Olson CM, Jr., Anguita J, Osborne BA (2009) Phosphorylation of Nur77 by the MEK-ERK-RSK cascade induces mitochondrial translocation and apoptosis in T cells. J Immunol 183:3268-3277.
10. Li H, et al. (2000) Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3. Science 289:1159-1164. (Pubitemid 30650723)
11. Liu ZG, Smith SW, McLaughlin KA, Schwartz LM, Osborne BA (1994) Apoptotic signals delivered through the T-cell receptor of a T-cell hybrid require the immediate-early gene nur77. Nature 367:281-284. (Pubitemid 24051145)
12. Moll UM, Marchenko N, Zhang XK (2006) p53 and Nur77/TR3: Transcription factors that directly target mitochondria for cell death induction. Oncogene 25:4725-4743. (Pubitemid 44187622)
13. Winoto A, Littman DR (2002) Nuclear hormone receptors in T lymphocytes. Cell 109 (Suppl):S57-S66. (Pubitemid 34457852)
14. Woronicz JD, Calnan B, Ngo V, Winoto A (1994) Requirement for the orphan steroid receptor Nur77 in apoptosis of T-cell hybridomas. Nature 367:277-281. (Pubitemid 24051144)
15. Rajpal A, et al. (2003) Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan steroid receptor. EMBO J 22:6526-6536. (Pubitemid 38009600)
16. Brás A, Albar JP, Leonardo E, de Buitrago GG, Martínez-A C (2000) Ceramide-induced cell death is independent of the Fas/Fas ligand pathway and is prevented by Nur77 overexpression in A20 B cells. Cell Death Differ 7:262-271.
17. Suzuki S, et al. (2003) Nur77 as a survival factor in tumor necrosis factor signaling. Proc Natl Acad Sci USA 100:8276-8280. (Pubitemid 36842535)
18. Osborne BA, et al. (1994) Identification of genes induced during apoptosis in T lymphocytes. Immunol Rev 142:301-320.
19. Moran AE, et al. (2011) T cell receptor signal strength in Treg and iNKT cell development-demonstrated by a novelfluorescent reportermouse. J ExpMed 208:1279-1289.
20. Cunningham NR, et al. (2006) Immature CD4+CD8+ thymocytes and mature T cells regulate Nur77 distinctly in response to TCR stimulation. J Immunol 177:6660-6666. (Pubitemid 44715029)
21. Liston A, et al. (2004) Generalized resistance to thymic deletion in the NOD mouse; a polygenic trait characterized by defective induction of Bim. Immunity 21:817-830. (Pubitemid 39626672)
22. Zucchelli S, et al. (2005) Defective central tolerance induction in NOD mice: genomics and genetics. Immunity 22:385-396. (Pubitemid 40387479)
23. Lee SL, et al. (1995) Unimpaired thymic and peripheral T cell death in mice lacking the nuclear receptor NGFI-B (Nur77). Science 269:532-535.
24. Cheng LE, Chan FK, Cado D, Winoto A (1997) Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell apoptosis. EMBO J 16:1865-1875. (Pubitemid 27170948)
25. Judkowski V, et al. (2001) Identification of MHC class II-restricted peptide ligands, including a glutamic acid decarboxylase 65 sequence, that stimulate diabetogenic T cells from transgenic BDC2.5 nonobese diabetic mice. J Immunol 166:908-917. (Pubitemid 32060245)
26. Barnden MJ, Allison J, Heath WR, Carbone FR (1998) Defective TCR expression in transgenic mice constructed using cDNA-based alpha- and beta-chain genes under the control of heterologous regulatory elements. Immunol Cell Biol 76:34-40. (Pubitemid 28194695)
27. Kurts C, et al. (1996) Constitutive class I-restricted exogenous presentation of self antigens in vivo. J Exp Med 184:923-930. (Pubitemid 26313550)
28. Apostolou I, Sarukhan A, Klein L, von Boehmer H (2002) Origin of regulatory T cells with known specificity for antigen. Nat Immunol 3:756-763.
29. Jordan MS, et al. (2001) Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol 2:283-284.
30. Kawahata K, et al. (2002) Generation of CD4(+)CD25(+) regulatory T cells from autoreactive T cells simultaneously with their negative selection in the thymus and from nonautoreactive T cells by endogenous TCR expression. J Immunol 168:4399-4405. (Pubitemid 34441340)
31. Walker LS, Chodos A, Eggena M, Dooms H, Abbas AK (2003) Antigen-dependent proliferation of CD4+ CD25+ regulatory T cells in vivo. J Exp Med 198:249-258. (Pubitemid 36992178)
32. Bonasio R, et al. (2006) Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus. Nat Immunol 7:1092-1100. (Pubitemid 44420654)
33. Liston A, Lesage S, Wilson J, Peltonen L, Goodnow CC (2003) Aire regulates negative selection of organ-specific T cells. Nat Immunol 4:350-354. (Pubitemid 36432317)
34. Smith KA (2004) The quantal theory of how the immune system discriminates between "self and non-self." Med Immunol 3:3.
35. Burchill MA, et al. (2008) Linked T cell receptor and cytokine signaling govern the development of the regulatory T cell repertoire. Immunity 28:112-121.
36. Chen W, et al. (2003) Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198: 1875-1886. (Pubitemid 38032120)
37. Hill JA, et al. (2007) Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity 27:786-800. (Pubitemid 350110546)
38. Pei L, et al. (2006) NR4A orphan nuclear receptors are transcriptional regulators of hepatic glucose metabolism. Nat Med 12:1048-1055. (Pubitemid 44353386)
39. Warburg O, Christian W (1941) Isolation and crystallization of fermentation enzyme enolase. Biochem Z 310:384-421.
40. Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science 324:1029-1033.
41. Pearen MA, Muscat GE (2010) Minireview: Nuclear hormone receptor 4A signaling: Implications for metabolic disease. Mol Endocrinol 24:1891-1903.
42. Pols TW, Bonta PI, de Vries CJ (2007) NR4A nuclear orphan receptors: Protective in vascular disease? Curr Opin Lipidol 18:515-520. (Pubitemid 47462203)
43. Sekiya T, et al. (2011) The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4+ T cells. Nat Commun 2:269.
44. Baldwin TA, Hogquist KA (2007) Transcriptional analysis of clonal deletion in vivo. J Immunol 179:837-844.
45. Kasler HG, Verdin E (2007) Histone deacetylase 7 functions as a key regulator of genes involved in both positive and negative selection of thymocytes. Mol Cell Biol 27:5184-5200. (Pubitemid 47068292)
46. Shi LZ, et al. (2011) HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med 208:1367-1376.
47. Katz JD, Wang B, Haskins K, Benoist C, Mathis D (1993) Following a diabetogenic T cell from genesis through pathogenesis. Cell 74:1089-1100. (Pubitemid 23289465)
48. Bouillet P, et al. (1999) Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 286:1735-1738. (Pubitemid 129515880)
49. Yamagata T, Mathis D, Benoist C (2004) Self-reactivity in thymic double-positive cells commits cells to a CD8 alpha alpha lineage with characteristics of innate immune cells. Nat Immunol 5:597-605. (Pubitemid 38811884)