Aire and T cell development

Current Opinion in Immunology

Volumn 23, Issue 2, 2011, Pages 198-206

  Anderson, Mark S ^a   Su, Maureen A ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIBODY; AUTOIMMUNE REGULATOR PROTEIN; BETA INTERFERON; CHEMOKINE RECEPTOR CCR4; CHEMOKINE RECEPTOR CCR7; CHOLINERGIC RECEPTOR; CYTOKINE; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; OVALBUMIN; PROINSULIN; T LYMPHOCYTE ANTIGEN; T LYMPHOCYTE RECEPTOR; TISSUE SPECIFIC SELF ANTIGEN; UNCLASSIFIED DRUG;

ANTIBODY PRODUCTION; ANTIGEN EXPRESSION; ANTIGEN PRESENTING CELL; AUTOIMMUNE DISEASE; AUTOIMMUNITY; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL SELECTION; DENDRITIC CELL; EPITHELIUM CELL; GENE DISRUPTION; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE FUNCTION; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; LYMPHOCYTE DIFFERENTIATION; MEDULLARY THYMIC EPITHELIAL CELL; MYASTHENIA GRAVIS; PROMOTER REGION; REGULATORY T LYMPHOCYTE; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; T LYMPHOCYTE; THYMOCYTE; THYMOMA; VARIABLE NUMBER OF TANDEM REPEAT;

ANIMALS; AUTOIMMUNITY; CELL DIFFERENTIATION; EPITHELIAL CELLS; HUMANS; T-LYMPHOCYTES; THYMUS GLAND; TRANSCRIPTION FACTORS;

EID: 79953097064     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coi.2010.11.007     Document Type: Review

References (79)

1. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy. Nat Genet 1997, 17:399-403. The Finnish-German, APECED Consortium.
2. Nagamine K., Peterson P., Scott H.S., Kudoh J., Minoshima S., Heino M., Krohn K.J.E., Lalioti M.D., Mullis P.E., Antonarakis S.E., et al. Positional cloning of the APECED gene. Nat Genet 1997, 17:393-398.
3. Perheentupa J. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab 2006, 91:2843-2850.
4. 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.
5. Gotter J., Brors B., Hergenhahn M., Kyewski B. Medullary epithelial cells of the human thymus express a highly diverse selection of tissue-specific genes colocalized in chromosomal clusters. J Exp Med 2004, 199:155-166.
6. Bjorses P., Pelto-Huikko M., Kaukonen J., Aaltonen J., Peltonen L., Ulmanen I. Localization of the APECED protein in distinct nuclear structures. Hum Mol Genet 1999, 8:259-266.
7. Anderson M.S., Venanzi E.S., Klein L., Chen Z., Berzins S.P., Turley S.J., von Boehmer H., Bronson R., Dierich A., Benoist C., et al. Projection of an immunological self shadow within the thymus by the aire protein. Science 2002, 298:1395-1401.
8. Derbinski J., Gäbler J., Brors B., Tierling S., Jonnakuty S., Hergenhahn M., Peltonen L., Walter J., Kyewski B. Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels. J Exp Med 2005, 202:33-45.
9. Mathis D., Benoist C. Aire. Annu Rev Immunol 2009, 27:287-312.
10. Peterson P., Org T., Rebane A. Transcriptional regulation by AIRE: molecular mechanisms of central tolerance. Nat Rev Immunol 2008, 8:948-957.
11. Gardner J.M., Fletcher A.L., Anderson M.S., Turley S.J. AIRE in the thymus and beyond. Curr Opin Immunol 2009, 21:582-589.
12. Michels A.W., Gottlieb P.A. Autoimmune polyglandular syndromes. Nat Rev Endocrinol 2010, 6:270-277.
13. Derbinski J., Gabler J., Brors B., Tierling S., Jonnakuty S., Hergenhahn M., Peltonen L., Walter J., Kyewski B. Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels. J Exp Med 2005, 202:33-45.
14. Villaseñor J., Besse W., Benoist C., Mathis D. Ectopic expression of peripheral-tissue antigens in the thymic epithelium: probabilistic, monoallelic, misinitiated. Proc Natl Acad Sci USA 2008, 105:15854-15859.
15. Gardner J.M., Devoss J.J., Friedman R.S., Wong D.J., Tan Y.X., Zhou X., Johannes K.P., Su M.A., Chang H.Y., Krummel M.F., et al. Deletional tolerance mediated by extrathymic Aire-expressing cells. Science 2008, 321:843-847.
16. Guerau-de-Arellano M., Mathis D., Benoist C. Transcriptional impact of Aire varies with cell type. Proc Natl Acad Sci USA 2008, 105:14011-14016.
17. Abramson J., Giraud M., Benoist C., Mathis D. Aire's partners in the molecular control of immunological tolerance. Cell 2010, 140:123-135.
18. Venanzi E.S., Melamed R., Mathis D., Benoist C. The variable immunological self: genetic variation and nongenetic noise in Aire-regulated transcription. Proc Natl Acad Sci USA 2008, 105:15860-15865.
19. Johnnidis J.B., Venanzi E.S., Taxman D.J., Ting J.P., Benoist C.O., Mathis D.J. Chromosomal clustering of genes controlled by the aire transcription factor. Proc Natl Acad Sci USA 2005, 102:7233-7238.
20. Org T., Chignola F., Hetenyi C., Gaetani M., Rebane A., Liiv I., Maran U., Mollica L., Bottomley M.J., Musco G., et al. The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression. EMBO Rep 2008, 9:370-376.
21. Chakravarty S., Zeng L., Zhou M.-M. Structure and site-specific recognition of histone H3 by the PHD finger of human autoimmune regulator. Structure 2009, 17:670-679.
22. Koh A.S., Kuo A.J., Park S.Y., Cheung P., Abramson J., Bua D., Carney D., Shoelson S.E., Gozani O., Kingston R.E., 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.
23. Chignola F., Gaetani M., Rebane A., Org T., Mollica L., Zucchelli C., Spitaleri A., Mannella V., Peterson P., Musco G. The solution structure of the first PHD finger of autoimmune regulator in complex with non-modified histone H3 tail reveals the antagonistic role of H3R2 methylation. Nucleic Acids Res 2009, 37:2951-2961.
24. Musco G., Peterson P. PHD finger of autoimmune regulator: an epigenetic link between the histone modifications and tissue-specific antigen expression in thymus. Epigenetics 2008, 3:310-314.
25. Koh A.S., Kingston R.E., Benoist C., Mathis D. Global relevance of Aire binding to hypomethylated lysine-4 of histone-3. Proc Natl Acad Sci USA 2010, 107:13016-13021.
26. Liiv I., Rebane A., Org T., Saare M., Maslovskaja J., Kisand K., Juronen E., Valmu L., Bottomley M.J., Kalkkinen N., et al. DNA-PK contributes to the phosphorylation of AIRE: importance in transcriptional activity. Biochim Biophys Acta 2008, 1783:74-83.
27. Halonen M., Kangas H., Ruppell T., Ilmarinen T., Ollila J., Kolmer M., Vihinen M., Palvimo J., Saarela J., Ulmanen I., et al. APECED-causing mutations in AIRE reveal the functional domains of the protein. Hum Mutat 2004, 23:245-257.
28. Anderson M.S., Venanzi E.S., Chen Z., Berzins S.P., Benoist C., Mathis D. The cellular mechanism of Aire control of T cell tolerance. Immunity 2005, 23:227-239.
29. Liston A., Lesage S., Wilson J., Peltonen L., Goodnow C.C. Aire regulates negative selection of organ-specific T cells. Nat Immunol 2003, 4:350-354.
30. Liston A., Gray D.H.D., Lesage S., Fletcher A.L., Wilson J., Webster K.E., Scott H.S., Boyd R.L., Peltonen L., Goodnow C.C. Gene dosage-limiting role of aire in thymic expression, clonal deletion, and organ-specific autoimmunity. J Exp Med 2004, 200:1015-1026.
31. Su M.A., Giang K., Zumer K., Jiang H., Oven I., Rinn J.L., Devoss J.J., Johannes K.P., Lu W., Gardner J., et al. Mechanisms of an autoimmunity syndrome in mice caused by a dominant mutation in Aire. J Clin Invest 2008, 118:1712-1726.
32. Liston A., Gray D.H., Lesage S., Fletcher A.L., Wilson J., Webster K.E., Scott H.S., Boyd R.L., Peltonen L., Goodnow C.C. Gene dosage--limiting role of Aire in thymic expression, clonal deletion, and organ-specific autoimmunity. J Exp Med 2004, 200:1015-1026.
33. Kedzierska K., Valkenburg S.A., Guillonneau C., Hubert F.-X., Cukalac T., Curtis J.M., Stambas J., Scott H.S., Kedzierski L., Venturi V., et al. Diversity and clonotypic composition of influenza-specific CD8+ TCR repertoires remain unaltered in the absence of Aire. Eur J Immunol 2010, 40:849-858.
34. Devoss J., Hou Y., Johannes K., Lu W., Liou G.I., Rinn J., Chang H., Caspi R., Fong L., Anderson M.S. Spontaneous autoimmunity prevented by thymic expression of a single self-antigen. J Exp Med 2006, 203:2727-2735.
35. Gavanescu I., Kessler B., Ploegh H., Benoist C., Mathis D. Loss of Aire-dependent thymic expression of a peripheral tissue antigen renders it a target of autoimmunity. Proc Natl Acad Sci USA 2007, 104:4583-4587.
36. Hou Y., Devoss J., Dao V., Kwek S., Simko J.P., McNeel D.G., Anderson M.S., Fong L. An aberrant prostate antigen-specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans. J Clin Invest 2009.
37. Shum A.K., DeVoss J., Tan C.L., Hou Y., Johannes K., O'Gorman C.S., Jones K.D., Sochett E.B., Fong L., Anderson M.S. Identification of an autoantigen demonstrates a link between interstitial lung disease and a defect in central tolerance. Sci Transl Med 2009, 1:9ra20.
38. Fletcher A.L., Seach N., Reiseger J.J., Lowen T.E., Hammett M.V., Scott H.S., Boyd R.L. Reduced thymic Aire expression and abnormal NF-kappa B2 signaling in a model of systemic autoimmunity. J Immunol 2009, 182:2690-2699.
39. Cai C.Q., Zhang T., Breslin M.B., Giraud M., Lan M.S. Both polymorphic VNTR and AIRE modulate differential expression of insulin in human thymic epithelial cells. Diabetes 2010.
40. Pugliese A., Zeller M., Fernandez A., Zalcberg L.J., Bartlett R.J., Ricordi C., Pietropaolo M., Eisenbarth G.S., Bennett S.T., Patel D.D. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nat Genet 1997, 15:293-297.
41. Vafiadis P., Bennett S.T., Todd J.A., Nadeau J., Grabs R., Goodyer C.G., Wickramasinghe S., Colle E., Polychronakos C. Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus. Nat Genet 1997, 15:289-292.
42. Giraud M., Taubert R., Vandiedonck C., Ke X., Lévi-Strauss M., Pagani F., Baralle F.E., Eymard B., Tranchant C., Gajdos P., et al. An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus. Nature 2007, 448:934-937.
43. Guerau-de-Arellano M., Martinic M., Benoist C., Mathis D. Neonatal tolerance revisited: a perinatal window for Aire control of autoimmunity. J Exp Med 2009, 206:1245-1252.
44. Cheng M.H., Fan U., Grewal N., Barnes M., Mehta A., Taylor S., Husebye E.S., Murphy E.J., Anderson M.S. Acquired autoimmune polyglandular syndrome, thymoma, and an AIRE defect. N Engl J Med 2010, 362:764-766.
45. Marx A., Hohenberger P., Hoffmann H., Pfannschmidt J., Schnabel P., Hofmann H.S., Wiebe K., Schalke B., Nix W., Gold R., et al. The autoimmune regulator AIRE in thymoma biology: autoimmunity and beyond. J Thorac Oncol 2010, 5:S266-S272.
46. Gallegos A.M., Bevan M.J. Central tolerance to tissue-specific antigens mediated by direct and indirect antigen presentation. J Exp Med 2004, 200:1039-1049.
47. Hinterberger M., Aichinger M., da Costa O.P., Voehringer D., Hoffmann R., Klein L. Autonomous role of medullary thymic epithelial cells in central CD4(+) T cell tolerance. Nat Immunol 2010, 11:512-519.
48. Koble C., Kyewski B. The thymic medulla: a unique microenvironment for intercellular self-antigen transfer. J Exp Med 2009, 206:1505-1513.
49. Nedjic J., Aichinger M., Emmerich J., Mizushima N., Klein L. Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature 2008, 455:396-400.
50. Laan M., Kisand K., Kont V., Möll K., Tserel L., Scott H.S., Peterson P. 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.
51. Ueno T., Saito F., Gray D.H., Kuse S., Hieshima K., Nakano H., Kakiuchi T., Lipp M., Boyd R.L., Takahama Y. CCR7 signals are essential for cortex-medulla migration of developing thymocytes. J Exp Med 2004, 200:493-505.
52. Li J., Li Y., Yao J.-Y., Jin R., Zhu M.-Z., Qian X.-P., Zhang J., Fu Y.-X., Wu L., Zhang Y., et al. Developmental pathway of CD4+CD8- medullary thymocytes during mouse ontogeny and its defect in Aire-/- mice. Proc Natl Acad Sci USA 2007, 104:18175-18180.
53. Lienenklaus S., Cornitescu M., Zietara N., Łyszkiewicz M., Gekara N., Jabłónska J., Edenhofer F., Rajewsky K., Bruder D., Hafner M., et al. Novel reporter mouse reveals constitutive and inflammatory expression of IFN-beta in vivo. J Immunol 2009, 183:3229-3236.
54. Gillard G.O., Dooley J., Erickson M., Peltonen L., Farr A.G. Aire-dependent alterations in medullary thymic epithelium indicate a role for Aire in thymic epithelial differentiation. J Immunol 2007, 178:3007-3015.
55. Zuklys S., Balciunaite G., Agarwal A., Fasler-Kan E., Palmer E., Hollander G.A. Normal Thymic Architecture and Negative Selection Are Associated with Aire Expression, the Gene Defective in the Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED). J Immunol 2000, 165:1976-1983.
56. Ramsey C., Winqvist O., Puhakka L., Halonen M., Moro A., Kampe O., Eskelin P., Pelto-Huikko M., Peltonen L. Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. Hum Mol Genet 2002, 11:397-409.
57. Yano M., Kuroda N., Han H., Meguro-Horike M., Nishikawa Y., Kiyonari H., Maemura K., Yanagawa Y., Obata K., Takahashi S., 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.
58. Milicevic Z., Milicevic N.M., Laan M., Peterson P., Kisand K., Scott H.S., Westermann J. Ultrastructure of medullary thymic epithelial cells of autoimmune regulator (Aire)-deficient mice. Immunol Cell Biol 2010, 88:50-56.
59. Dooley J., Erickson M., Farr A.G. Alterations of the medullary epithelial compartment in the Aire-deficient thymus: implications for programs of thymic epithelial differentiation. J Immunol 2008, 181:5225-5232.
60. Kuroda N., Mitani T., Takeda N., Ishimaru N., Arakaki R., Hayashi Y., Bando Y., Izumi K., Takahashi T., Nomura T., et al. Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient mice. J Immunol 2005, 174:1862-1870.
61. Daniely D., Kern J., Cebula A., Ignatowicz L. Diversity of TCRs on natural Foxp3+ T cells in mice lacking Aire expression. J Immunol 2010, 184:6865-6873.
62. Ryan K.R., Lawson C.A., Lorenzi A.R., Arkwright P.D., Isaacs J.D., Lilic D. CD4+CD25+ T-regulatory cells are decreased in patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. J Allergy Clin Immunol 2005, 116:1158-1159.
63. Kekalainen E., Tuovinen H., Joensuu J., Gylling M., Franssila R., Pontynen N., Talvensaari K., Perheentupa J., Miettinen A., Arstila T.P. A Defect of Regulatory T Cells in Patients with Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy. J Immunol 2007, 178:1208-1215.
64. Wolff A.S.B., Oftedal B.E.V., Kisand K., Ersvaer E., Lima K., Husebye E.S. Flow cytometry study of blood cell subtypes reflects autoimmune and inflammatory processes in autoimmune polyendocrine syndrome type I. Scand J Immunol 2010, 71:459-467.
65. Laakso S.M., Laurinolli T.-T., Rossi L.H., Lehtoviita A., Sairanen H., Perheentupa J., Kekäläinen E., Arstila T.P. Regulatory T cell defect in APECED patients is associated with loss of naive FOXP3(+) precursors and impaired activated population. J Autoimmun 2010.
66. Gäbler J., Arnold J., Kyewski B. Promiscuous gene expression and the developmental dynamics of medullary thymic epithelial cells. Eur J Immunol 2007, 37:3363-3372.
67. Gray D., Abramson J., Benoist C., Mathis D. Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire. J Exp Med 2007.
68. White A.J., Nakamura K., Jenkinson W.E., Saini M., Sinclair C., Seddon B., Narendran P., Pfeffer K., Nitta T., Takahama Y., et al. Lymphotoxin signals from positively selected thymocytes regulate the terminal differentiation of medullary thymic epithelial cells. J Immunol 2010.
69. Nishikawa Y., Hirota F., Yano M., Kitajima H., Miyazaki J., Kawamoto H., Mouri Y., Matsumoto M. Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation. J Exp Med 2010, 207:963-971.
70. Chin R.K., Lo J.C., Kim O., Blink S.E., Christiansen P.A., Peterson P., Wang Y., Ware C., Fu Y.X. Lymphotoxin pathway directs thymic Aire expression. Nat Immunol 2003, 4:1121-1127.
71. Zhu M., Chin R.K., Christiansen P.A., Lo J.C., Liu X., Ware C., Siebenlist U., Fu Y.-X. NF-{kappa}B2 is required for the establishment of central tolerance through an Aire-dependent pathway. J Clin Invest 2006, 116:2964-2971.
72. Martins V.C., Boehm T., Bleul C.C. Ltbetar signaling does not regulate Aire-dependent transcripts in medullary thymic epithelial cells. J Immunol 2008, 181:400-407.
73. Venanzi E.S., Gray D.H.D., Benoist C., Mathis D. Lymphotoxin pathway and Aire influences on thymic medullary epithelial cells are unconnected. J Immunol 2007, 179:5693-5700.
74. Rossi S.W., Kim M.-Y., Leibbrandt A., Parnell S.M., Jenkinson W.E., Glanville S.H., McConnell F.M., Scott H.S., Penninger J.M., Jenkinson E.J., 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.
75. Seach N., Ueno T., Fletcher A.L., Lowen T., Mattesich M., Engwerda C.R., Scott H.S., Ware C.F., Chidgey A.P., Gray D.H.D., et al. The lymphotoxin pathway regulates Aire-independent expression of ectopic genes and chemokines in thymic stromal cells. J Immunol 2008, 180:5384-5392.
76. Akiyama T., Shimo Y., Yanai H., Qin J., Ohshima D., Maruyama Y., Asaumi Y., Kitazawa J., Takayanagi H., Penninger J.M., et al. The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity 2008, 29:423-437.
77. Hikosaka Y., Nitta T., Ohigashi I., Yano K., Ishimaru N., Hayashi Y., Matsumoto M., Matsuo K., Penninger J.M., Takayanagi H., et al. The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. Immunity 2008, 29:438-450.
78. Irla M., Hugues S., Gill J., Nitta T., Hikosaka Y., Williams I.R., Hubert F.-X., Scott H.S., Takahama Y., Holländer G.A., et al. Autoantigen-specific interactions with CD4+ thymocytes control mature medullary thymic epithelial cell cellularity. Immunity 2008, 29:451-463.
79. White A.J., Withers D.R., Parnell S.M., Scott H.S., Finke D., Lane P.J.L., Jenkinson E.J., Anderson G. Sequential phases in the development of Aire-expressing medullary thymic epithelial cells involve distinct cellular input. Eur J Immunol 2008, 38:942-947.