Regeneration of the aged thymus by a single transcription factor

Development (Cambridge)

Volumn 141, Issue 8, 2014, Pages 1627-1637

  Bredenkamp, Nicholas ^a,b   Nowell, Craig S ^a,c   Clare Blackburn, C ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c EPFL   (Switzerland)

Author keywords

FOXN1; Mouse; Organ regeneration; Thymic involution

Indexed keywords

CYCLIN D1; FIBROBLAST GROWTH FACTOR RECEPTOR 2; FORKHEAD TRANSCRIPTION FACTOR; INTERLEUKIN 2 RECEPTOR ALPHA; KERATINOCYTE GROWTH FACTOR; TAMOXIFEN; TRANSCRIPTION FACTOR FORKHEAD BOX N1; UNCLASSIFIED DRUG;

ARTICLE; CELL PROLIFERATION; GENE EXPRESSION; GENE EXPRESSION PROFILING; HOUSEKEEPING GENE; IMMUNE SYSTEM; IMMUNOBLOTTING; IMMUNOCOMPETENCE; LYMPHOCYTE DIFFERENTIATION; MICROENVIRONMENT; NONHUMAN; PRE T LYMPHOCYTE; PRIORITY JOURNAL; PROTEIN FUNCTION; THYMUS; THYMUS FUNCTION; TISSUE REGENERATION; TRANSGENE; UPREGULATION;

FOXN1; MOUSE; ORGAN REGENERATION; THYMIC INVOLUTION;

AGING; ANIMALS; CELL PROLIFERATION; CELLULAR MICROENVIRONMENT; EPITHELIAL CELLS; FORKHEAD TRANSCRIPTION FACTORS; LYMPHOCYTE COUNT; MICE; MICE, TRANSGENIC; MODELS, ANIMAL; PHENOTYPE; REGENERATION; STEM CELLS; T-LYMPHOCYTES; THYMUS GLAND; UP-REGULATION;

EID: 84898727454     PISSN: 09501991     EISSN: 14779129     Source Type: Journal    
DOI: 10.1242/dev.103614     Document Type: Article

References (72)

1. Adolfsson, J., Månsson, R., Buza-Vidas, N., Hultquist, A., Liuba, K., Jensen, C. T., Bryder, D., Yang, L., Borge, O. -J., Thoren, L. A. M. et al. (2005). Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential. Cell 121, 295-306.
2. Akiyama, T., Shimo, Y., Yanai, H., Qin, J., Ohshima, D., Maruyama, Y., Asaumi, Y., Kitazawa, J., Takayanagi, H., Penninger, J. M. et al. (2008). The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity 29, 423-437.
3. Allman, D., Sambandam, A., Kim, S., Miller, J. P., Pagan, A., Well, D., Meraz, A. and Bhandoola, A. (2003). Thymopoiesis independent of common lymphoid progenitors. Nat. Immunol. 4, 168-174.
4. Alpdogan, O., Hubbard, V. M., Smith, O. M., Patel, N., Lu, S., Goldberg, G. L., Gray, D. H., Feinman, J., Kochman, A. A., Eng, J. M. et al. (2006). Keratinocyte growth factor (KGF) is required for postnatal thymic regeneration. Blood 107, 2453-2460.
5. 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. (2002). Projection of an immunological self shadow within the thymus by the aire protein. Science 298, 1395-1401.
6. Antonica, F., Kasprzyk, D. F., Opitz, R., Iacovino, M., Liao, X. -H., Dumitrescu, A. M., Refetoff, S., Peremans, K., Manto, M., Kyba, M. et al. (2012). Generation of functional thyroid from embryonic stem cells. Nature 491, 66-71.
7. Bennett, A. R., Farley, A., Blair, N. F., Gordon, J., Sharp, L. and Blackburn, C. C. (2002). Identification and characterization of thymic epithelial progenitor cells. Immunity 16, 803-814.
8. Blackburn, C. C., Augustine, C. L., Li, R., Harvey, R. P., Malin, M. A., Boyd, R. L., Miller, J. F. and Morahan, G. (1996). The nu gene acts cell-autonomously and is required for differentiation of thymic epithelial progenitors. Proc. Natl. Acad. Sci. U. S. A. 93, 5742-5746.
9. Boursalian, T. E., Golob, J., Soper, D. M., Cooper, C. J. and Fink, P. J. (2004). Continued maturation of thymic emigrants in the periphery. Nat. Immunol. 5, 418-425.
10. Budd, R. C., Cerottini, J. C., Horvath, C., Bron, C., Pedrazzini, T., Howe, R. C. and MacDonald, H. R. (1987). Distinction of virgin and memory T lymphocytes. Stable acquisition of the Pgp-1 glycoprotein concomitant with antigenic stimulation. J. Immunol. 138, 3120-3129.
11. Calderon, L. and Boehm, T. (2012). Synergistic, context-dependent, and hierarchical functions of epithelial components in thymic microenvironments. Cell 149, 159-172.
12. Candi, E., Rufini, A., Terrinoni, A., Giamboi-Miraglia, A., Lena, A. M., Mantovani, R., Knight, R. and Melino, G. (2007). DeltaNp63regulatesthymic development through enhanced expression of FgfR2 and Jag2. Proc. Natl. Acad. Sci. U. S. A. 104, 11999-12004.
13. Chen, L., Xiao, S. and Manley, N. R. (2009). Foxn1 is required to maintain the postnatal thymic microenvironment in a dosage-sensitive manner. Blood 113, 567-574.
14. Chinn, I. K., Blackburn, C. C., Manley, N. R. and Sempowski, G. D. (2012). Changes in primary lymphoid organs with aging. Semin. Immunol. 24, 309-320.
15. Cirillo, L. A., Lin, F. R., Cuesta, I., Friedman, D., Jarnik, M. and Zaret, K. S. (2002). Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4. Mol. Cell 9, 279-289.
16. DeMonte, L., Porcellini, S., Tafi, E., Sheridan, J., Gordon, J., Depreter, M., Blair, N., Panigada, M., Sanvito, F., Merati, B. et al. (2007). EVA regulates thymic stromal organisation and early thymocyte development. Biochem. Biophys. Res. Commun. 356, 334-340.
17. Depreter, M. G. L., Blair, N. F., Gaskell, T. L., Nowell, C. S., Davern, K., Pagliocca, A., Stenhouse, F. H., Farley, A. M., Fraser, A., Vrana, J. et al. (2008). Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells. Proc. Natl. Acad. Sci. U. S. A. 105, 961-966.
18. Derbinski, J., Gabler, J., Brors, B., Tierling, S., Jonnakuty, S., Hergenhahn, M., Peltonen, L., Walter, J. and Kyewski, B. (2005). Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels. J. Exp. Med. 202, 33-45.
19. Dudakov, J. A., Hanash, A. M., Jenq, R. R., Young, L. F., Ghosh, A., Singer, N. V., West, M. L., Smith, O. M., Holland, A. M., Tsai, J. J. et al. (2012). Interleukin-22 drives endogenous thymic regeneration in mice. Science 336, 91-95.
20. Fiorini, E., Ferrero, I., Merck, E., Favre, S., Pierres, M., Luther, S. A. and MacDonald, H. R. (2008). Cutting edge: thymic crosstalk regulates delta-like 4 expression on cortical epithelial cells. J. Immunol. 181, 8199-8203.
21. Garfin, P. M., Min, D., Bryson, J. L., Serwold, T., Edris, B., Blackburn, C. C., Richie, E. R., Weinberg, K. I., Manley, N. R., Sage, J. et al. (2013). Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression. J. Exp. Med. 210, 1087-1097.
22. Gordon, J., Xiao, S., Hughes, B., III, Su, D. -M., Navarre, S. P., Condie, B. G. and Manley, N. R. (2007). Specific expression of lacZ and cre recombinase in fetal thymic epithelial cells by multiplex gene targeting at the Foxn1 locus. BMC Dev. Biol. 7, 69.
23. Goronzy, J. J. and Weyand, C. M. (2005). T cell development and receptor diversity during aging. Curr. Opin. Immunol. 17, 468-475.
24. Graf, T. and Enver, T. (2009). Forcing cells to change lineages. Nature 462, 587-594.
25. Gray, D. H. D., Seach, N., Ueno, T., Milton, M. K., Liston, A., Lew, A. M., Goodnow, C. C. and Boyd, R. L. (2006). Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells. Blood 108, 3777-3785.
26. Gray, D. H. D., Fletcher, A. L., Hammett, M., Seach, N., Ueno, T., Young, L. F., Barbuto, J., Boyd, R. L. and Chidgey, A. P. (2008). Unbiased analysis, enrichment and purification of thymic stromal cells. J. Immunol. Methods 329, 56-66.
27. Griffith, A. V., Fallahi, M., Venables, T. and Petrie, H. T. (2012). Persistent degenerative changes in thymic organ function revealed by an inducible model of organ regrowth. Aging Cell 11, 169-177.
28. Holland, A. M. and van den Brink, M. R. M. (2009). Rejuvenationof the aging Tcell compartment. Curr. Opin. Immunol. 21, 454-459.
29. Honey, K., Nakagawa, T., Peters, C. and Rudensky, A. (2002). Cathepsin L regulates CD4+ T cell selection independently of its effect on invariant chain: a role in the generation of positively selecting peptide ligands. J. Exp. Med. 195, 1349-1358.
30. Hozumi, K., Mailhos, C., Negishi, N., Hirano, K.-i., Yahata, T., Ando, K., Zuklys, S., Hollander, G. A., Shima, D. T. and Habu, S. (2008). Delta-like4isindispensable in thymic environment specific for T cell development. J. Exp. Med. 205, 2507-2513.
31. Itoi, M., Kawamoto, H., Katsura, Y. and Amagai, T. (2001). Two distinct steps of immigration of haematopoietic progenitors into the early thymus anlage. Int. Immunol. 13, 1203-1211.
32. Janes, S. M., Ofstad, T. A., Campbell, D. H., Watt, F. M. and Prowse, D. M. (2004). Transient activation of FOXN1 in keratinocytes induces a transcriptional programme that promotes terminal differentiation: contrasting roles of FOXN1 and Akt. J. Cell Sci. 117, 4157-4168.
33. Koch, U., Fiorini, E., Benedito, R., Besseyrias, V., Schuster-Gossler, K., Pierres, M., Manley, N. R., Duarte, A., Macdonald, H. R. and Radtke, F. (2008). Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T cell lineage commitment. J. Exp. Med. 205, 2515-2523.
34. Laufer, T. M., DeKoning, J., Markowitz, J. S., Lo, D. and Glimcher, L. H. (1996). Unopposed positive selection and autoreactivity in mice expressing class II MHC only on thymic cortex. Nature 383, 81-85.
35. Lynch, H. E., Goldberg, G. L., Chidgey, A., Van den Brink, M. R. M., Boyd, R. and Sempowski, G. D. (2009). Thymic involution and immune reconstitution. Trends Immunol. 30, 366-373.
36. Mackall, C. L., Punt, J. A., Morgan, P., Farr, A. G. and Gress, R. E. (1998). Thymic function in young/old chimeras: substantial thymic T cell regenerative capacity despite irreversible age-associated thymic involution. Eur. J. Immunol. 28, 1886-1893.
37. Markert, M. L., Devlin, B. H., Chinn, I. K. and McCarthy, E. A. (2009). Thymus transplantation in complete DiGeorge anomaly. Immunol. Res. 44, 61-70.
38. Mathis, D. and Benoist, C. (2009). Aire. Annu. Rev. Immunol. 27, 287-312.
39. Miller, J. F. A. P. (1961). Immunological function of the thymus. Lancet 278, 748-749.
40. Min, H., Montecino-Rodriguez, E. and Dorshkind, K. (2006). Reassessing the role of growth hormone and sex steroids in thymic involution. Clin. Immunol. 118, 117-123.
41. Min, D., Panoskaltsis-Mortari, A., Kuro-o, M., Hollander, G. A., Blazar, B. R. and Weinberg, K. I. (2007). Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging. Blood 109, 2529-2537.
42. Morris, L., Gordon, J. and Blackburn, C. C. (2006). Identification of a tandem duplicated array in the Rhox alpha locus on mouse chromosome X. Mamm. Genome 17, 178-187.
43. Naquet, P., Naspetti, M. and Boyd, R. (1999). Development, organization and function of the thymic medulla in normal, immunodeficient or autoimmune mice. Semin. Immunol. 11, 47-55.
44. Nehls, M., Kyewski, B., Messerle, M., Waldschutz, R., Schuddekopf, K., Smith, A. J. H. and Boehm, T. (1996). Two genetically separable steps in the differentiation of thymic epithelium. Science 272, 886-889.
45. Nowell, C. S., Bredenkamp, N., Tetelin, S., Jin, X., Tischner, C., Vaidya, H., Sheridan, J. M., Stenhouse, F. H., Heussen, R., Smith, A. J. H. et al. (2011). Foxn1 regulates lineage progression in cortical and medullary thymic epithelial cells but is dispensable for medullary sublineage divergence. PLoS Genet. 7, e1002348.
46. Olsen, N. J., Olson, G., Viselli, S. M., Gu, X. and Kovacs, W. J. (2001). Androgen receptors in thymic epithelium modulate thymus size and thymocyte development. Endocrinology 142, 1278-1283.
47. Ortman, C. L., Dittmar, K. A., Witte, P. L. and Le, P. T. (2002). Molecular characterization of the mouse involuted thymus: aberrations in expression of transcription regulators in thymocyte and epithelial compartments. Int. Immunol. 14, 813-822.
48. Reiser, H. and Schneeberger, E. E. (1994). The costimulatory molecule B7 is expressed in the medullary region of the murine thymus. Immunology 81, 532-537.
49. Revest, J. M., Suniara, R. K., Kerr, K., Owen, J. J. and Dickson, C. (2001). Development of the thymus requires signaling through the fibroblast growth factor receptor R2-IIIb. J. Immunol. 167, 1954-1961.
50. Robles, A. I., Larcher, F., Whalin, R. B., Murillas, R., Richie, E. R., Gimenez-Conti, I. B., Jorcano, J. L. and Conti, C. J. (1996). Expression of cyclin D1 in epithelial tissues of transgenic mice results in epidermal hyperproliferation and severe thymic hyperplasia. Proc. Natl. Acad. Sci. U. S. A. 93, 7634-7638.
51. Rodewald, H. -R., Ogawa, M., Haller, C., Waskow, C. and DiSanto, J. P. (1997). Pro-thymocyte expansion by c-kit and the common cytokine receptor gamma chain is essential for repertoire formation. Immunity 6, 265-272.
52. Sambandam, A., Maillard, I., Zediak, V. P., Xu, L., Gerstein, R. M., Aster, J. C., Pear, W. S. and Bhandoola, A. (2005). Notch signaling controls the generation and differentiation of early T lineage progenitors. Nat. Immunol. 6, 663-670.
53. Schlake, T., Schorpp, M., Nehls, M. and Boehm, T. (1997). The nude gene encodes a sequence-specific DNA binding protein with homologs in organisms that lack an anticipatory immune system. Proc. Natl. Acad. Sci. U. S. A. 94, 3842-3847.
54. Seguin, C. A., Draper, J. S., Nagy, A. and Rossant, J. (2008). Establishment of endoderm progenitors by SOX transcription factor expression in human embryonic stem cells. Cell Stem Cell 3, 182-195.
55. Sempowski, G. D., Gooding, M. E., Liao, H. X., Le, P. T. and Haynes, B. F. (2002). T cell receptor excision circle assessment of thymopoiesis in aging mice. Mol. Immunol. 38, 841-848.
56. Senoo, M., Pinto, F., Crum, C. P. and McKeon, F. (2007). p63 Is essential for the proliferative potential of stem cells in stratified epithelia. Cell 129, 523-536.
57. Sun, L., Guo, J., Brown, R., Amagai, T., Zhao, Y. and Su, D. -M. (2010). Declining expression of a single epithelial cell-autonomous gene accelerates age-related thymic involution. Aging Cell 9, 347-357.
58. Takahashi, K. and Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676.
59. Trampont, P. C., Tosello-Trampont, A. -C., Shen, Y., Duley, A. K., Sutherland, A. E., Bender, T. P., Littman, D. R. and Ravichandran, K. S. (2010). CXCR4 acts as a costimulator during thymic beta-selection'. Nat. Immunol. 11, 162-170.
60. Tsai, P. T., Lee, R. A. and Wu, H. (2003). BMP4 acts upstreamof FGF in modulating thymic stroma and regulating thymopoiesis. Blood 102, 3947-3953.
61. Tykocinski, L. -O., Sinemus, A. and Kyewski, B. (2008). The thymus medulla slowly yields its secrets. Ann. N. Y. Acad. Sci. 1143, 105-122.
62. Van Den Berg, T. K., Hasbold, J., Renardel De Lavalette, C., Dopp, E. A., Dijkstra, C. D. and Klaus, G. G. B. (1996). Properties of mouse CD40: differential expression of CD40 epitopes on dendritic cells and epithelial cells. Immunology 88, 294-300.
63. van den Brink, M. R. M., Alpdogan, O. and Boyd, R. L. (2004). Strategies to enhance T-cell reconstitution in immunocompromised patients. Nat. Rev. Immunol. 4, 856-867.
64. Wallace, H. A. C., Marques-Kranc, F., Richardson, M., Luna-Crespo, F., Sharpe, J. A., Hughes, J., Wood, W. G., Higgs, D. R. and Smith, A. J. H. (2007). Manipulating the mouse genome to engineer precise functional syntenic replacements with human sequence. Cell 128, 197-209.
65. Wallin, J., Eibel, H., Neubuser, A., Wilting, J., Koseki, H. and Balling, R. (1996). Pax1 is expressed during development of the thymus epithelium and is required for normal T-cell maturation. Development 122, 23-30.
66. Weintraub, H., Tapscott, S. J., Davis, R. L., Thayer, M. J., Adam, M. A., Lassar, A. B. and Miller, A. D. (1989). Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proc. Natl. Acad. Sci. U. S. A. 86, 5434-5438.
67. Weng, N. -P. (2006). Aging of the immune system: how much can the adaptive immune system adapt? Immunity 24, 495-499.
68. Williams, K. M., Lucas, P. J., Bare, C. V., Wang, J., Chu, Y. -W., Tayler, E., Kapoor, V. and Gress, R. E. (2008). CCL25 increases thymopoiesis after androgen withdrawal. Blood 112, 3255-3263.
69. Zaret, K. S. and Carroll, J. S. (2011). Pioneer transcription factors: establishing competence for gene expression. Genes Dev. 25, 2227-2241.
70. Zhou, Q., Brown, J., Kanarek, A., Rajagopal, J. and Melton, D. A. (2008). In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455, 627-632.
71. Zlotoff, D. A., Sambandam, A., Logan, T. D., Bell, J. J., Schwarz, B. A. and Bhandoola, A. (2010). CCR7 and CCR9 together recruit hematopoietic progenitors to the adult thymus. Blood 115, 1897-1905.
72. Zook, E. C., Krishack, P. A., Zhang, S., Zeleznik-Le, N. J., Firulli, A. B., Witte, P. L. and Le, P. T. (2011). Overexpression of Foxn1 attenuates age-associated thymic involution and prevents the expansion of peripheral CD4 memory T cells. Blood 118, 5723-5731.