Adult thymic epithelial cell (TEC) progenitors and TEC stem cells: Models and mechanisms for TEC development and maintenance

European Journal of Immunology

Volumn 45, Issue 11, 2015, Pages 2985-2993

  Hamazaki, Yoko ^a  

^a KYOTO UNIVERSITY   (Japan)

Author keywords

TEC maintenance; Thymic epithelial cells (TECs); Thymic epithelial stem cells; Thymic involution; Thymic ontogeny

Indexed keywords

CLAUDIN 3; CLAUDIN 4; PODOPLANIN; TIGHT JUNCTION PROTEIN;

ADULT; ASYMMETRIC CELL DIVISION; AUTOIMMUNITY; CELL DIFFERENTIATION; CELL DIVISION; CELL LINEAGE; CELL MATURATION; EPIDERMAL STEM CELL; EPITHELIUM CELL; HUMAN; KERATINOCYTE; MESENCHYMAL STEM CELL; NONHUMAN; ONTOGENY; PERINATAL PERIOD; PRIORITY JOURNAL; PROGENY; SHORT SURVEY; STEM CELL; STEM CELL NICHE; THYMIC EPITHELIAL CELL; THYMOCYTE; ANIMAL; CYTOLOGY; EMBRYOLOGY; GROWTH, DEVELOPMENT AND AGING; IMMUNOLOGY; THYMUS;

ANIMALS; CELL DIFFERENTIATION; EPITHELIAL CELLS; HUMANS; STEM CELLS; THYMUS GLAND;

EID: 84951569365     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201545844     Document Type: Short Survey

References (91)

1. Manley, N. R., Richie, E. R., Blackburn, C. C., Condie, B. G. and Sage, J., Structure and function of the thymic microenvironment. Front Biosci. (Landmark Ed) 2011. 16: 2461-2477.
2. van Ewijk, W., Shores, E. W. and Singer, A., Crosstalk in the mouse thymus. Immunol. Today 1994. 15: 214-217.
3. Lynch, H. E., Goldberg, G. L., Chidgey, A., Van den Brink, M. R., Boyd, R. and Sempowski, G. D., Thymic involution and immune reconstitution. Trends Immunol. 2009. 30: 366-373.
4. Dooley, J. and Liston, A., Molecular control over thymic involution: from cytokines and microRNA to aging and adipose tissue. Eur. J. Immunol. 2012. 42: 1073-1079.
5. Rodewald, H. R., Paul, S., Haller, C., Bluethmann, H. and Blum, C., Thymus medulla consisting of epithelial islets each derived from a single progenitor. Nature 2001. 414: 763-768.
6. Hamazaki, Y., Fujita, H., Kobayashi, T., Choi, Y., Scott, H. S., Matsumoto, M. and Minato, N., Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin. Nat. Immunol. 2007. 8: 304-311.
7. Rossi, S. W., Jenkinson, W. E., Anderson, G. and Jenkinson, E. J., Clonal analysis reveals a common progenitor for thymic cortical and medullary epithelium. Nature 2006. 441: 988-991.
8. Shakib, S., Desanti, G. E., Jenkinson, W. E., Parnell, S. M., Jenkinson, E. J. and Anderson, G., Checkpoints in the development of thymic cortical epithelial cells. J. Immunol. 2009. 182: 130-137.
9. Anderson, G. and Takahama, Y., Thymic epithelial cells: working class heroes for T cell development and repertoire selection. Trends Immunol. 2012. 33: 256-263.
10. Roberts, N. A., White, A. J., Jenkinson, W. E., Turchinovich, G., Nakamura, K., Withers, D. R., McConnell, F. M. et al., Rank signaling links the development of invariant gammadelta T cell progenitors and Aire(+) medullary epithelium. Immunity 2012. 36: 427-437.
11. Rossi, S. W., Kim, M. Y., Leibbrandt, A., Parnell, S. M., Jenkinson, W. E., Glanville, S. H., McConnell, F. M. 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.
12. Hikosaka, Y., Nitta, T., Ohigashi, I., Yano, K., Ishimaru, N., Hayashi, Y., Matsumoto, M. et al., The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. Immunity 2008. 29: 438-450.
13. Irla, M., Hugues, S., Gill, J., Nitta, T., Hikosaka, Y., Williams, I. R., Hubert, F. X. et al., Autoantigen-specific interactions with CD4+ thymocytes control mature medullary thymic epithelial cell cellularity. Immunity 2008. 29: 451-463.
14. Mathis, D. and Benoist, C., Aire. Annu. Rev. Immunol. 2009. 27: 287-312.
15. Aaltonen, J., Björses, P., Perheentupa, J., Kuitunen, N. H., Palotie, A., Peltonen, L., Lee, Y. S. et al., An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat. Genet. 1997. 17: 399-403.
16. Nagamine, K., Peterson, P., Scott, H. S., Kudoh, J., Minoshima, S., Heino, M., Krohn, K. J. et al., Positional cloning of the APECED gene. Nat. Genet. 1997. 17: 393-398.
17. Anderson, M. S., Venanzi, E. S., Klein, L., Chen, Z., Berzins, S. P., Turley, S. J., von Boehmer, H. et al., Projection of an immunological self shadow within the thymus by the aire protein. Science 2002. 298: 1395-1401.
18. Akiyama, T., Maeda, S., Yamane, S., Ogino, K., Kasai, M., Kajiura, F., Matsumoto, M. et al., Dependence of self-tolerance on TRAF6-directed development of thymic stroma. Science 2005. 308: 248-251.
19. Kajiura, F., Sun, S., Nomura, T., Izumi, K., Ueno, T., Bando, Y., Kuroda, N. et al., NF-kappa B-inducing kinase establishes self-tolerance in a thymic stroma-dependent manner. J. Immunol. 2004. 172: 2067-2075.
20. Kuroda, N., Mitani, T., Takeda, N., Ishimaru, N., Arakaki, R., Hayashi, Y., Bando, Y. et al., Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient mice. J. Immunol. 2005. 174: 1862-1870.
21. Akiyama, T., Shimo, Y., Yanai, H., Qin, J., Ohshima, D., Maruyama, Y., Asaumi, Y. 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.
22. Ramsey, C., Winqvist, O., Puhakka, L., Halonen, M., Moro, A., Kampe, O., Eskelin, P. et al., Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. Hum. Mol. Genet. 2002. 11: 397-409.
23. Gray, D. H., Seach, N., Ueno, T., Milton, M. K., Liston, A., Lew, A. M., Goodnow, C. C. et al., Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells. Blood 2006. 108: 3777-3785.
24. Gillard, G. O. and Farr, A. G., Features of medullary thymic epithelium implicate postnatal development in maintaining epithelial heterogeneity and tissue-restricted antigen expression. J. Immunol. 2006. 176: 5815-5824.
25. Gabler, J., Arnold, J. and Kyewski, B., Promiscuous gene expression and the developmental dynamics of medullary thymic epithelial cells. Eur. J. Immunol. 2007. 37: 3363-3372.
26. Gray, D., Abramson, J., Benoist, C. and Mathis, D., Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire. J. Exp. Med. 2007. 204: 2521-2528.
27. Nishikawa, Y., Nishijima, H., Matsumoto, M., Morimoto, J., Hirota, F., Takahashi, S., Luche, H. et al., Temporal lineage tracing of Aire-expressing cells reveals a requirement for Aire in their maturation program. J. Immunol. 2014. 192: 2585-2592.
28. Dumont-Lagace, M., Brochu, S., St-Pierre, C. and Perreault, C., Adult thymic epithelium contains nonsenescent label-retaining cells. J. Immunol. 2014. 192: 2219-2226.
29. Swann, J. B. and Boehm, T., Back to the beginning-the quest for thymic epithelial stem cells. Eur. J. Immunol. 2007. 37: 2364-2366.
30. Sekai, M., Hamazaki, Y. and Minato, N., Medullary thymic epithelial stem cells maintain a functional thymus to ensure lifelong central T cell tolerance. Immunity 2014. 41: 753-761.
31. Ucar, A., Ucar, O., Klug, P., Matt, S., Brunk, F., Hofmann, T. G. and Kyewski, B., Adult thymus contains FoxN1(-) epithelial stem cells that are bipotent for medullary and cortical thymic epithelial lineages. Immunity 2014. 41: 257-269.
32. Wong, K., Lister, N. L., Barsanti, M., Lim, J. M., Hammett, M. V., Khong, D. M., Siatskas, C. et al., Multilineage potential and self-renewal define an epithelial progenitor cell population in the adult thymus. Cell Rep. 2014. 8: 1198-1209.
33. Blackburn, C. C., Manley, N. R., Palmer, D. B., Boyd, R. L., Anderson, G. and Ritter, M. A., One for all and all for one: thymic epithelial stem cells and regeneration. Trends Immunol. 2002. 23: 391-395.
34. Gordon, J., Wilson, V. A., Blair, N. F., Sheridan, J., Farley, A., Wilson, L., Manley, N. R. et al., Functional evidence for a single endodermal origin for the thymic epithelium. Nat. Immunol. 2004. 5: 546-553.
35. Tsukita, S. and Furuse, M., Claudin-based barrier in simple and stratified cellular sheets. Curr. Opin. Cell Biol. 2002. 14: 531-536.
36. Tamura, A. and Tsukita, S., Paracellular barrier and channel functions of TJ claudins in organizing biological systems: advances in the field of barriology revealed in knockout mice. Semin. Cell Dev. Biol. 2014. 36: 177-185.
37. Ripen, A. M., Nitta, T., Murata, S., Tanaka, K. and Takahama, Y., Ontogeny of thymic cortical epithelial cells expressing the thymoproteasome subunit beta5t. Eur. J. Immunol. 2011. 41: 1278-1287.
38. Baik, S., Jenkinson, E. J., Lane, P. J., Anderson, G. and Jenkinson, W. E., Generation of both cortical and Aire(+) medullary thymic epithelial compartments from CD205(+) progenitors. Eur. J. Immunol. 2013. 43: 589-594.
39. Ohigashi, I., Zuklys, S., Sakata, M., Mayer, C. E., Zhanybekova, S., Murata, S., Tanaka, K. et al., Aire-expressing thymic medullary epithelial cells originate from beta5t-expressing progenitor cells. Proc. Natl. Acad. Sci. USA 2013. 110: 9885-9890.
40. Ribeiro, A. R., Rodrigues, P. M., Meireles, C., Di Santo, J. P. and Alves, N. L., Thymocyte selection regulates the homeostasis of IL-7-expressing thymic cortical epithelial cells in vivo. J. Immunol. 2013. 191: 1200-1209.
41. Peterson, P. and Laan, M., Bipotency of thymic epithelial progenitors comes in sequence. Eur. J. Immunol. 2013. 43: 580-583.
42. Alves, N. L., Takahama, Y., Ohigashi, I., Ribeiro, A. R., Baik, S., Anderson, G. and Jenkinson, W. E., Serial progression of cortical and medullary thymic epithelial microenvironments. Eur. J. Immunol. 2014. 44: 16-22.
43. Klug, D. B., Carter, C., Gimenez-Conti, I. B. and Richie, E. R., Cutting edge: thymocyte-independent and thymocyte-dependent phases of epithelial patterning in the fetal thymus. J. Immunol. 2002. 169: 2842-2845.
44. Jenkinson, W. E., Rossi, S. W., Jenkinson, E. J. and Anderson, G., Development of functional thymic epithelial cells occurs independently of lymphostromal interactions. Mech. Dev. 2005. 122: 1294-1299.
45. Roberts, N. A., Desanti, G. E., Withers, D. R., Scott, H. R., Jenkinson, W. E., Lane, P. J., Jenkinson, E. J. et al., Absence of thymus crosstalk in the fetus does not preclude hematopoietic induction of a functional thymus in the adult. Eur. J. Immunol. 2009. 39: 2395-2402.
46. Nowell, C. S., Bredenkamp, N., Tetelin, S., Jin, X., Tischner, C., Vaidya, H., Sheridan, J. M. et al., Foxn1 regulates lineage progression in cortical and medullary thymic epithelial cells but is dispensable for medullary sublineage divergence. PLoS Genet. 2011. 7: e1002348.
47. Frank, J., Pignata, C., Panteleyev, A. A., Prowse, D. M., Baden, H., Weiner, L., Gaetaniello, L. et al., Exposing the human nude phenotype. Nature 1999. 398: 473-474.
48. Nehls, M., Pfeifer, D., Schorpp, M., Hedrich, H. and Boehm, T., New member of the winged-helix protein family disrupted in mouse and rat nude mutations. Nature 1994. 372: 103-107.
49. Jenkinson, W. E., Jenkinson, E. J. and Anderson, G., Differential requirement for mesenchyme in the proliferation and maturation of thymic epithelial progenitors. J. Exp. Med. 2003. 198: 325-332.
50. Roberts, N. and Horsley, V., Developing stratified epithelia: lessons from the epidermis and thymus. Wiley Interdiscip. Rev. Dev. Biol. 2014. 3: 389-402.
51. Bonfanti, P., Claudinot, S., Amici, A. W., Farley, A., Blackburn, C. C. and Barrandon, Y., Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells. Nature 2010. 466: 978-982.
52. White, A. J., Nakamura, K., Jenkinson, W. E., Saini, M., Sinclair, C., Seddon, B., Narendran, P. et al., Lymphotoxin signals from positively selected thymocytes regulate the terminal differentiation of medullary thymic epithelial cells. J. Immunol. 2010. 185: 4769-4776.
53. Yano, M., Kuroda, N., Han, H., Meguro-Horike, M., Nishikawa, Y., Kiyonari, H., Maemura, K. 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.
54. Wang, X., Laan, M., Bichele, R., Kisand, K., Scott, H. S. and Peterson, P., Post-Aire maturation of thymic medullary epithelial cells involves selective expression of keratinocyte-specific autoantigens. Front. Immunol. 2012. 3: 19.
55. Wada, N., Nishifuji, K., Yamada, T., Kudoh, J., Shimizu, N., Matsumoto, M., Peltonen, L. et al., Aire-dependent thymic expression of desmoglein 3, the autoantigen in pemphigus vulgaris, and its role in T-cell tolerance. J. Invest. Dermatol. 2011. 131: 410-417.
56. Williams, S. E., Beronja, S., Pasolli, H. A. and Fuchs, E., Asymmetric cell divisions promote Notch-dependent epidermal differentiation. Nature 2011. 470: 353-358.
57. Furuse, M., Hata, M., Furuse, K., Yoshida, Y., Haratake, A., Sugitani, Y, Noda, T. et al., Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J. Cell Biol. 2002. 156: 1099-1111.
58. Depreter, M. G., Blair, N. F., Gaskell, T. L., Nowell, C. S., Davern, K., Pagliocca, A., Stenhouse, F. H. et al., Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells. Proc. Natl. Acad. Sci. USA 2008. 105: 961-966.
59. Bennett, A. R., Farley, A., Blair, N. F., Gordon, J., Sharp, L. and Blackburn, C. C., Identification and characterization of thymic epithelial progenitor cells. Immunity 2002. 16: 803-814.
60. Gill, J., Malin, M., Hollander, G. A. and Boyd, R., Generation of a complete thymic microenvironment by MTS24(+) thymic epithelial cells. Nat. Immunol. 2002. 3: 635-642.
61. Itoi, M., Kawamoto, H., Katsura, Y. and Amagai, T., Two distinct steps of immigration of hematopoietic progenitors into the early thymus anlage. Int. Immunol. 2001. 13: 1203-1211.
62. Jenkinson, W. E., Bacon, A., White, A. J., Anderson, G. and Jenkinson, E. J., An epithelial progenitor pool regulates thymus growth. J. Immunol. 2008. 181: 6101-6108.
63. Corbeaux, T., Hess, I., Swann, J. B., Kanzler, B., Haas-Assenbaum, A. and Boehm, T., Thymopoiesis in mice depends on a Foxn1-positive thymic epithelial cell lineage. Proc. Natl. Acad. Sci. USA 2010. 107: 16613-16618.
64. Osada, M., Singh, V. J., Wu, K., Sant'Angelo, D. B. and Pezzano, M., Label retention identifies a multipotent mesenchymal stem cell-like population in the postnatal thymus. PLoS One 2013. 8: e83024.
65. Waghmare, S. K., Bansal, R., Lee, J., Zhang, Y. V., McDermitt, D. J. and Tumbar, T., Quantitative proliferation dynamics and random chromosome segregation of hair follicle stem cells. EMBO J. 2008. 27: 1309-1320.
66. Bleul, C. C., Corbeaux, T., Reuter, A., Fisch, P., Monting, J. S. and Boehm, T., Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. Nature 2006. 441: 992-996.
67. Klug, D. B., Carter, C., Crouch, E., Roop, D., Conti, C. J. and Richie, E. R., Interdependence of cortical thymic epithelial cell differentiation and T-lineage commitment. Proc. Natl. Acad. Sci. USA 1998. 95: 11822-11827.
68. Onder, L., Nindl, V., Scandella, E., Chai, Q., Cheng, H. W., Caviezel-Firner, S., Novkovic, M. et al., Alternative NF-kappaB signaling regulates mTEC differentiation from podoplanin-expressing presursors in the cortico-medullary junction. Eur. J. Immunol. 2015. 45: 2218-2231.
69. Shanley, D. P., Aw, D., Manley, N. R. and Palmer, D. B., An evolutionary perspective on the mechanisms of immunosenescence. Trends Immunol. 2009. 30: 374-381.
70. Franckaert, D., Schlenner, S. M., Heirman, N., Gill, J., Skogberg, G., Ekwall, O., Put, K. et al., Premature thymic involution is independent of structural plasticity of the thymic stroma. Eur. J. Immunol. 2015. 45: 1535-1547.
71. Dudakov, J. A., Khong, D. M., Boyd, R. L. and Chidgey, A. P., Feeding the fire: the role of defective bone marrow function in exacerbating thymic involution. Trends Immunol. 2010. 31: 191-198.
72. Chinn, I. K., Blackburn, C. C., Manley, N. R. and Sempowski, G. D., Changes in primary lymphoid organs with aging. Semin. Immunol. 2012. 24: 309-320.
73. Palmer, D. B., The effect of age on thymic function. Front. Immunol. 2013. 4: 316.
74. Griffith, A. V., Fallahi, M., Venables, T. and Petrie, H. T., Persistent degenerative changes in thymic organ function revealed by an inducible model of organ regrowth. Aging Cell 2012. 11: 169-177.
75. Steinmann, G. G., Klaus, B. and Muller-Hermelink, H. K., The involution of the ageing human thymic epithelium is independent of puberty. A morphometric study. Scand. J. Immunol. 1985. 22: 563-575.
76. Rode, I. and Boehm, T., Regenerative capacity of adult cortical thymic epithelial cells. Proc. Natl. Acad. Sci. USA 2012. 109: 3463-3468.
77. Sutherland, J. S., Spyroglou, L., Muirhead, J. L., Heng, T. S., Prieto-Hinojosa, A., Prince, H. M., Chidgey, A. P. et al., Enhanced immune system regeneration in humans following allogeneic or autologous hemopoietic stem cell transplantation by temporary sex steroid blockade. Clin. Cancer Res. 2008. 14: 1138-1149.
78. Velardi, E., Tsai, J. J., Holland, A. M., Wertheimer, T., Yu, V. W., Zakrzewski, J. L., Tuckett, A. Z. et al., Sex steroid blockade enhances thymopoiesis by modulating Notch signaling. J. Exp. Med. 2014. 211: 2341-2349.
79. Hozumi, K., Mailhos, C., Negishi, N., Hirano, K., Yahata, T., Ando, K., Zuklys, S. et al., Delta-like 4 is indispensable in thymic environment specific for T cell development. J. Exp. Med. 2008. 205: 2507-2513.
80. Fletcher, A. L., Lowen, T. E., Sakkal, S., Reiseger, J. J., Hammett, M. V., Seach, N., Scott, H. S. et al., Ablation and regeneration of tolerance-inducing medullary thymic epithelial cells after cyclosporine, cyclophosphamide, and dexamethasone treatment. J. Immunol. 2009. 183: 823-831.
81. Metzger, T. C., Khan, I. S., Gardner, J. M., Mouchess, M. L., Johannes, K. P., Krawisz, A. K., Skrzypczynska, K. M. et al., Lineage tracing and cell ablation identify a post-Aire-expressing thymic epithelial cell population. Cell Rep. 2013. 5: 166-179.
82. Snippert, H. J. and Clevers, H., Tracking adult stem cells. EMBO Rep. 2011. 12: 113-122.
83. Bowie, M. B., McKnight, K. D., Kent, D. G., McCaffrey, L., Hoodless, P. A. and Eaves, C. J., Hematopoietic stem cells proliferate until after birth and show a reversible phase-specific engraftment defect. J. Clin. Invest. 2006. 116: 2808-2816.
84. Bowie, M. B., Kent, D. G., Dykstra, B., McKnight, K. D., McCaffrey, L., Hoodless, P. A. and Eaves, C. J., Identification of a new intrinsically timed developmental checkpoint that reprograms key hematopoietic stem cell properties. Proc. Natl. Acad. Sci. USA 2007. 104: 5878-5882.
85. Sun, J., Ramos, A., Chapman, B., Johnnidis, J. B., Le, L., Ho, Y. J., Klein, A. et al., Clonal dynamics of native haematopoiesis. Nature 2014. 514: 322-327.
86. Busch, K., Klapproth, K., Barile, M., Flossdorf, M., Holland-Letz, T., Schlenner, S. M., Reth, M. et al., Fundamental properties of unperturbed haematopoiesis from stem cells in vivo. Nature 2015. 518: 542-546.
87. Ortman, C. L., Dittmar, K. A., Witte, P. L. and Le, P. T., Molecular characterization of the mouse involuted thymus: aberrations in expression of transcription regulators in thymocyte and epithelial compartments. Int. Immunol. 2002. 14: 813-822.
88. Zook, E. C., Krishack, P. A., Zhang, S., Zeleznik-Le, N. J., Firulli, A. B., Witte, P. L. and Le, P. T., Overexpression of Foxn1 attenuates age-associated thymic involution and prevents the expansion of peripheral CD4 memory T cells. Blood 2011. 118: 5723-5731.
89. Chen, L., Xiao, S. and Manley, N. R., Foxn1 is required to maintain the postnatal thymic microenvironment in a dosage-sensitive manner. Blood 2009. 113: 567-574.
90. Bredenkamp, N., Ulyanchenko, S., O'Neill, K. E., Manley, N. R., Vaidya, H. J. and Blackburn, C. C., An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts. Nat. Cell Biol. 2014. 16: 902-908.
91. Jin, X., Nowell, C. S., Ulyanchenko, S., Stenhouse, F. H. and Blackburn, C. C., Long-term persistence of functional thymic epithelial progenitor cells in vivo under conditions of low FOXN1 expression. PLoS One 2014. 9: e114842.