Induction of central tolerance by the factor Aire: Molecular and epigenetic regulation;Induction de la tolérance centrale dans le thymus par le facteur de transcription Aire

Medecine/Sciences

Volumn 31, Issue 8-9, 2015, Pages 742-747

  Lopes, Noëlla ^a   Ferrier, Pierre ^a   Irla, Magali ^a  

^a CENTRE D IMMUNOLOGIE DE MARSEILLE LUMINY   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOIMMUNE REGULATOR PROTEIN; TRANSCRIPTION FACTOR;

GENETIC EPIGENESIS; GENETICS; HUMAN; IMMUNOLOGICAL TOLERANCE;

CENTRAL TOLERANCE; EPIGENESIS, GENETIC; HUMANS; TRANSCRIPTION FACTORS;

EID: 84941210788     PISSN: 07670974     EISSN: 19585381     Source Type: Journal    
DOI: 10.1051/medsci/20153108012     Document Type: Article

References (45)

1. Derbinski J, Schulte A, Kyewski B, Klein L. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat Immunol 2001; 2: 1032-1039.
2. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell 2008; 133: 775-787.
3. Anderson MS, Venanzi ES, Klein L, et al. Projection of an immunological self shadow within the thymus by the aire protein. Science 2002; 298: 1395-1401.
4. Hamazaki Y, Fujita H, Kobayashi T, et al. Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin. Nat Immunol 2007; 8: 304-311.
5. Sekai M, Hamazaki Y, Minato N. Medullary thymic epithelial stem cells maintain a functional thymus to ensure lifelong central T cell tolerance. Immunity 2014; 41: 753-761.
6. Irla M, Hollander G, Reith W. Control of central self-Tolerance induction by autoreactive CD4+ thymocytes. Trends Immunol 2010; 31: 71-79.
7. Gray D, Abramson J, Benoist C, Mathis D. Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire. J Exp Med 2007; 204: 2521-2528.
8. Rossi SW, Kim MY, Leibbrandt A, et al. RANK signals from CD4+3- inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla. J Exp Med 2007; 204: 1267-1272.
9. Irla M. Cellules épithéliales médullaires thymiques exprimant Aire: acteurs clés dans l'induction de la tolérance des cellules T. Med Sci (Paris) 2012; 28: 146-149.
10. Irla M, Hugues S, Gill J, et al. Autoantigen-specific interactions with CD4+ thymocytes control mature medullary thymic epithelial cell cellularity. Immunity 2008; 29: 451-463.
11. Irla M, Guerri L, Guenot J, et al. Antigen recognition by autoreactive CD4+ thymocytes drives homeostasis of the thymic medulla. PLoS One 2012; 7: e52591.
12. Sansom SN, Shikama-Dorn N, Zhanybekova S, et al. Population and single-cell genomics reveal the Aire dependency, relief from Polycomb silencing, and distribution of self-antigen expression in thymic epithelia. Genome Res 2014; 24: 1918-1931.
13. Nishikawa Y, Hirota F, Yano M, et al. Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation. J Exp Med 2010; 207: 963-971.
14. Metzger TC, Khan IS, Gardner JM, et al. Lineage tracing and cell ablation identify a post-Aire-expressing thymic epithelial cell population. Cell Rep 2013; 5: 166-179.
15. Wang X, Laan M, Bichele R, et al. Post-Aire maturation of thymic medullary epithelial cells involves selective expression of keratinocyte-specific autoantigens. Front Immunol 2012; 3: 19.
16. Yano M, Kuroda N, Han H, et al. Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-Tolerance. J Exp Med 2008; 205: 2827-2838.
17. Watanabe N, Wang YH, Lee HK, et al. Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 2005; 436: 1181-1185.
18. Gillard GO, Dooley J, Erickson M, et al. Aire-dependent alterations in medullary thymic epithelium indicate a role for Aire in thymic epithelial differentiation. J Immunol 2007; 178: 3007-3015.
19. Dooley J, Erickson M, Farr AG. Alterations of the medullary epithelial compartment in the Aire-deficient thymus: implications for programs of thymic epithelial differentiation. J Immunol 2008; 181: 5225-5232.
20. Mathis D, Benoist C. A decade of AIRE. Nat Rev Immunol 2007; 7: 645-650.
21. Aaltonen J, Bjorses P. Cloning of the APECED gene provides new insight into human autoimmunity. Ann Med 1999; 31: 111-116.
22. Halonen M, Kangas H, Ruppell T, et al. APECED-causing mutations in AIRE reveal the functional domains of the protein. Hum Mutat 2004; 23: 245-257.
23. Ilmarinen T, Melen K, Kangas H, et al. The monopartite nuclear localization signal of autoimmune regulator mediates its nuclear import and interaction with multiple importin alpha molecules. FEBS J 2006; 273: 315-324.
24. Purohit S, Kumar PG, Laloraya M, She JX. Mapping DNA-binding domains of the autoimmune regulator protein. Biochem Biophys Res Commun 2005; 327: 939-944.
25. Zumer K, Low AK, Jiang H, et al. Unmodified histone H3K4 and DNA-dependent protein kinase recruit autoimmune regulator to target genes. Mol Cell Biol 2012; 32: 1354-1362.
26. Koh AS, Kuo AJ, Park SY, et al. Aire employs a histone-binding module to mediate immunological tolerance, linking chromatin regulation with organ-specific autoimmunity. Proc Natl Acad Sci USA 2008; 105: 15878-15883.
27. Org T, Chignola F, Hetényi C, et al. The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression. EMBO Rep 2008; 9: 370-376.
28. Gaetani M, Matafora V, Saare M, et al. AIRE-PHD fingers are structural hubs to maintain the integrity of chromatin-associated interactome. Nucleic Acids Res 2012; 40: 11756-11768.
29. Zumer K, Plemenitas A, Saksela K, Peterlin BM. Patient mutation in AIRE disrupts P-TEFb binding and target gene transcription. Nucleic Acids Res 2011; 39: 7908-7919.
30. Giraud M, Yoshida H, Abramson J, et al. Aire unleashes stalled RNA polymerase to induce ectopic gene expression in thymic epithelial cells. Proc Natl Acad Sci USA 2012; 109: 535-540.
31. Liiv I, Rebane A, Org T, et al. DNA-PK contributes to the phosphorylation of AIRE: importance in transcriptional activity. Biochim Biophys Acta 2008; 1783: 74-83.
32. Peterson P, Org T, Rebane A. Transcriptional regulation by AIRE: molecular mechanisms of central tolerance. Nat Rev Immunol 2008; 8: 948-957.
33. Rattay K, Claude J, Rezavandy E, et al. Homeodomain-interacting protein kinase 2, a novel autoimmune regulator interaction partner, modulates promiscuous gene expression in medullary thymic epithelial cells. J Immunol 2015; 194: 921-928.
34. Giraud M, Jmari N, Du L, et al. An RNAi screen for Aire cofactors reveals a role for Hnrnpl in polymerase release and Aire-activated ectopic transcription. Proc Natl Acad Sci USA 2014; 111: 1491-1496.
35. Anderson MS, Venanzi ES, Chen Z, et al. The cellular mechanism of Aire control of T cell tolerance. Immunity 2005; 23: 227-239.
36. Hinterberger M, Aichinger M, Prazeres da Costa O, et al. Autonomous role of medullary thymic epithelial cells in central CD4+ T cell tolerance. Nat Immunol 2010; 11: 512-519.
37. Aschenbrenner K, D'Cruz LM, Vollmann EH, et al. Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells. Nat Immunol 2007; 8: 351-358.
38. Lei Y, Ripen AM, Ishimaru N, et al. Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development. J Exp Med 2011; 208: 383-394.
39. Malchow S, Leventhal DS, Nishi S, et al. Aire-dependent thymic development of tumor-associated regulatory T cells. Science 2013; 339: 1219-1224.
40. Takahama Y. Journey through the thymus: stromal guides for T-cell development and selection. Nat Rev Immunol 2006; 6: 127-135.
41. Laan M, Kisand K, Kont V, et al. Autoimmune regulator deficiency results in decreased expression of CCR4 and CCR7 ligands and in delayed migration of CD4+ thymocytes. J Immunol 2009; 183: 7682-7691.
42. Ueno T, Hara K, Willis MS, et al. Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus. Immunity 2002; 16: 205-218.
43. Kurobe H, Liu C, Ueno T, et al. CCR7-dependent cortex-To-medulla migration of positively selected thymocytes is essential for establishing central tolerance. Immunity 2006; 24: 165-177.
44. Hubert FX, Kinkel SA, Davey GM, et al. Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance. Blood 2011; 118: 2462-2472.
45. Gardner JM, Metzger TC, McMahon EJ, et al. Extrathymic Aire-expressing cells are a distinct bone marrow-derived population that induce functional inactivation of CD4+ T cells. Immunity 2013; 39: 560-572.