MTORC2 in thymic epithelial cells controls thymopoiesis and T cell development

Journal of Immunology

Volumn 197, Issue 1, 2016, Pages 141-150

  Wang, Hong Xia ^a,b   Cheng, Joyce S ^b,c   Chu, Shuai ^a,b   Qiu, Yu Rong ^a   Zhong, Xiao Ping ^b  

^a SOUTHERN MEDICAL UNIVERSITY   (China)

^b DUKE UNIVERSITY MEDICAL CENTER   (United States)

^c TEMPLE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; PROTEIN RICTOR; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; CARRIER PROTEIN; LYMPHOCYTE ANTIGEN RECEPTOR; MULTIPROTEIN COMPLEX; RICTOR PROTEIN, MOUSE; TARGET OF RAPAMYCIN KINASE; TOR COMPLEX 2;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELL DIFFERENTIATION; CELL LINEAGE; CELL MATURATION; CONTROLLED STUDY; EMBRYO; EPITHELIUM CELL; GAMMA DELTA T LYMPHOCYTE; MOUSE; NATURAL KILLER CELL; NEWBORN; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE; THYMIC EPITHELIAL CELL; THYMOCYTE; THYMOPOIESIS; ANIMAL; C57BL MOUSE; CELL CULTURE; GENETICS; IMMUNOLOGY; KNOCKOUT MOUSE; LYMPHOCYTE SUBPOPULATION; LYMPHOPOIESIS; METABOLISM; PHYSIOLOGY; THYMUS;

ANIMALS; CARRIER PROTEINS; CELL DIFFERENTIATION; CELL LINEAGE; CELLS, CULTURED; EPITHELIAL CELLS; KILLER CELLS, NATURAL; LYMPHOCYTE SUBSETS; LYMPHOPOIESIS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MULTIPROTEIN COMPLEXES; RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA; RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA; T-LYMPHOCYTES; THYMUS GLAND; TOR SERINE-THREONINE KINASES;

EID: 84975252042     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1502698     Document Type: Article

References (54)

1. Fahl, S. P., F. Coffey, and D. L. Wiest. 2014. Origins of gd T cell effector subsets: A riddle wrapped in an enigma. J. Immunol. 193: 4289-4294.
2. Yang, Q., J. Jeremiah Bell, and A. Bhandoola. 2010. T-cell lineage determination. Immunol. Rev. 238: 12-22.
3. Anderson, G., and Y. Takahama. 2012. Thymic epithelial cells: working class heroes for T cell development and repertoire selection. Trends Immunol. 33: 256-263.
4. Nehls, M., B. Kyewski, M. Messerle, R. Waldschutz, K. Schuddekopf, A. J. Smith, and T. Boehm. 1996. Two genetically separable steps in the differentiation of thymic epithelium. Science 272: 886-889.
5. Su, D. M., S. Navarre, W. J. Oh, B. G. Condie, and N. R. Manley. 2003. A domain of Foxn1 required for crosstalk-dependent thymic epithelial cell differentiation. Nat. Immunol. 4: 1128-1135.
6. Anderson, M. S., E. S. Venanzi, L. Klein, Z. Chen, S. P. Berzins, S. J. Turley, H. von Boehmer, R. Bronson, A. Dierich, C. Benoist, and D. Mathis. 2002. Projection of an immunological self shadow within the thymus by the aire protein. Science 298: 1395-1401.
7. Klein, L., B. Kyewski, P. M. Allen, and K. A. Hogquist. 2014. Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see). Nat. Rev. Immunol. 14: 377-391.
8. Cowan, J. E., S. M. Parnell, K. Nakamura, J. H. Caamano, P. J. Lane, E. J. Jenkinson, W. E. Jenkinson, and G. Anderson. 2013. The thymic medulla is required for Foxp3+ regulatory but not conventional CD4+ thymocyte development. J. Exp. Med. 210: 675-681.
9. Perry, J. S., C. W. Lio, A. L. Kau, K. Nutsch, Z. Yang, J. I. Gordon, K. M. Murphy, and C. S. Hsieh. 2014. Distinct contributions of Aire and antigen-presenting-cell subsets to the generation of self-tolerance in the thymus. Immunity 41: 414-426.
10. Coquet, J. M., J. C. Ribot, N. Bąbała, S. Middendorp, G. van der Horst, Y. Xiao, J. F. Neves, D. Fonseca-Pereira, H. Jacobs, D. J. Pennington, et al. 2013. Epithelial and dendritic cells in the thymic medulla promote CD4+Foxp3+ regulatory T cell development via the CD27-CD70 pathway. J. Exp. Med. 210: 715-728.
11. Derbinski, J., A. Schulte, B. Kyewski, and L. Klein. 2001. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat. Immunol. 2: 1032-1039.
12. Laplante, M., and D. M. Sabatini. 2012. mTOR signaling in growth control and disease. Cell 149: 274-293.
13. O'Brien, T. F., and X. P. Zhong. 2012. The role and regulation of mTOR in Tlymphocyte function. Arch. Immunol. Ther. Exp. (Warsz.) 60: 173-181.
14. Gorentla, B. K., C. K. Wan, and X. P. Zhong. 2011. Negative regulation of mTOR activation by diacylglycerol kinases. Blood 117: 4022-4031.
15. Wu, J., J. Yang, K. Yang, H. Wang, B. Gorentla, J. Shin, Y. Qiu, L. G. Que, W. M. Foster, Z. Xia, et al. 2014. iNKT cells require TSC1 for terminal maturation and effector lineage fate decisions. J. Clin. Invest. 124: 1685-1698.
16. Shin, J., S. Wang, W. Deng, J. Wu, J. Gao, and X. P. Zhong. 2014. Mechanistic target of rapamycin complex 1 is critical for invariant natural killer T-cell development and effector function. Proc. Natl. Acad. Sci. USA 111: E776-E783.
17. Zeng, H., K. Yang, C. Cloer, G. Neale, P. Vogel, and H. Chi. 2013. mTORC1 couples immune signals and metabolic programming to establish Treg-cell function. Nature 499: 485-490.
18. Xie, D. L., J. Wu, Y. L. Lou, and X. P. Zhong. 2012. Tumor suppressor TSC1 is critical for T-cell anergy. Proc. Natl. Acad. Sci. USA 109: 14152-14157.
19. Lee, K., K. T. Nam, S. H. Cho, P. Gudapati, Y. Hwang, D. S. Park, R. Potter, J. Chen, E. Volanakis, and M. Boothby. 2012. Vital roles of mTOR complex 2 in Notch-driven thymocyte differentiation and leukemia. J. Exp. Med. 209: 713-728.
20. Hoshii, T., A. Kasada, T. Hatakeyama, M. Ohtani, Y. Tadokoro, K. Naka, T. Ikenoue, T. Ikawa, H. Kawamoto, H. J. Fehling, et al. 2014. Loss of mTOR complex 1 induces developmental blockage in early T-lymphopoiesis and eradicates T-cell acute lymphoblastic leukemia cells. Proc. Natl. Acad. Sci. USA 111: 3805-3810.
21. Yang, W., B. Gorentla, X. P. Zhong, and J. Shin. 2015. mTOR and its tight regulation for iNKT cell development and effector function. Mol. Immunol. 68(2 Pt C): 536-545.
22. Wang, H. X., J. Shin, S. Wang, B. Gorentla, X. Lin, J. Gao, Y. R. Qiu, and X. P. Zhong. 2016. mTORC1 in thymic epithelial cells is critical for thymopoiesis, T-cell generation, and temporal control of gdT17 development and TCRg/d recombination. PLoS Biol. 14: e1002370.
23. Magee, J. A., T. Ikenoue, D. Nakada, J. Y. Lee, K. L. Guan, and S. J. Morrison. 2012. Temporal changes in PTEN and mTORC2 regulation of hematopoietic stem cell self-renewal and leukemia suppression. Cell Stem Cell 11: 415-428.
24. Gordon, J., S. Xiao, B. Hughes, III, D. M. Su, S. P. Navarre, B. G. Condie, and N. R. Manley. 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.
25. Gray, D. H., A. L. Fletcher, M. Hammett, N. Seach, T. Ueno, L. F. Young, J. Barbuto, R. L. Boyd, and A. P. Chidgey. 2008. Unbiased analysis, enrichment and purification of thymic stromal cells. J. Immunol. Methods 329: 56-66.
26. Wang, H. X., Y. R. Qiu, and X. P. Zhong. 2016. Intercellular protein transfer from thymocytes to thymic epithelial cells. PLoS One 11: e0152641.
27. Chen, Y., X. Ci, B. Gorentla, S. A. Sullivan, J. C. Stone, W. Zhang, P. Pereira, J. Lu, and X. P. Zhong. 2012. Differential requirement of RasGRP1 for gd T cell development and activation. J. Immunol. 189: 61-71.
28. Shakib, S., G. E. Desanti, W. E. Jenkinson, S. M. Parnell, E. J. Jenkinson, and G. Anderson. 2009. Checkpoints in the development of thymic cortical epithelial cells. J. Immunol. 182: 130-137.
29. Nowell, C. S., N. Bredenkamp, S. Tetélin, X. Jin, C. Tischner, H. Vaidya, J. M. Sheridan, F. H. Stenhouse, R. Heussen, A. J. Smith, and C. C. Blackburn. 2011. Foxn1 regulates lineage progression in cortical and medullary thymic epithelial cells but is dispensable for medullary sublineage divergence. PLoS Genet. 7: e1002348.
30. Chien, Y. H., C. Meyer, and M. Bonneville. 2014. gd T cells: first line of defense and beyond. Annu. Rev. Immunol. 32: 121-155.
31. Born, W. K., M. Kemal Aydintug, and R. L. O'Brien. 2013. Diversity of gd Tcell antigens. Cell. Mol. Immunol. 10: 13-20.
32. Bonneville, M., R. L. O'Brien, and W. K. Born. 2010. gd T cell effector functions: A blend of innate programming and acquired plasticity. Nat. Rev. Immunol. 10: 467-478.
33. Haas, J. D., S. Ravens, S. Duber, I. Sandrock, L. Oberdörfer, E. Kashani, V. Chennupati, L. Föhse, R. Naumann, S. Weiss, et al. 2012. Development of interleukin-17-producing gd T cells is restricted to a functional embryonic wave. Immunity 37: 48-59.
34. Ribot, J. C., A. deBarros, D. J. Pang, J. F. Neves, V. Peperzak, S. J. Roberts, M. Girardi, J. Borst, A. C. Hayday, D. J. Pennington, and B. Silva-Santos. 2009. CD27 is a thymic determinant of the balance between interferon-g-and interleukin 17-producing gd T cell subsets. Nat. Immunol. 10: 427-436.
35. Nitta, T., R. Muro, Y. Shimizu, S. Nitta, H. Oda, Y. Ohte, M. Goto, R. Yanobu-Takanashi, T. Narita, H. Takayanagi, et al. 2015. The thymic cortical epithelium determines the TCR repertoire of IL-17-producing gdT cells. EMBO Rep. 16: 638-653.
36. Egawa, T., G. Eberl, I. Taniuchi, K. Benlagha, F. Geissmann, L. Hennighausen, A. Bendelac, and D. R. Littman. 2005. Genetic evidence supporting selection of the Va14i NKT cell lineage from double-positive thymocyte precursors. Immunity 22: 705-716.
37. Wu, J., J. Shin, D. Xie, H. Wang, J. Gao, and X. P. Zhong. 2014. Tuberous sclerosis 1 promotes invariant NKT cell anergy and inhibits invariant NKT cellmediated antitumor immunity. J. Immunol. 192: 2643-2650.
38. Prevot, N., K. Pyaram, E. Bischoff, J. M. Sen, J. D. Powell, and C. H. Chang. 2015. Mammalian target of rapamycin complex 2 regulates invariant NKT cell development and function independent of promyelocytic leukemia zinc-finger. J. Immunol. 194: 223-230.
39. Zhang, L., B. O. Tschumi, S. Corgnac, M. A. Ruegg, M. N. Hall, J. P. Mach, P. Romero, and A. Donda. 2014. Mammalian target of rapamycin complex 1 orchestrates invariant NKT cell differentiation and effector function. J. Immunol. 193: 1759-1765.
40. Lee, K., P. Gudapati, S. Dragovic, C. Spencer, S. Joyce, N. Killeen, M. A. Magnuson, and M. Boothby. 2010. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity 32: 743-753.
41. Delgoffe, G. M., K. N. Pollizzi, A. T. Waickman, E. Heikamp, D. J. Meyers, M. R. Horton, B. Xiao, P. F. Worley, and J. D. Powell. 2011. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat. Immunol. 12: 295-303.
42. Tang, F., Q. Wu, T. Ikenoue, K. L. Guan, Y. Liu, and P. Zheng. 2012. A critical role for Rictor in T lymphopoiesis. J. Immunol. 189: 1850-1857.
43. Jacobs, S. R., C. E. Herman, N. J. Maciver, J. A. Wofford, H. L. Wieman, J. J. Hammen, and J. C. Rathmell. 2008. Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J. Immunol. 180: 4476-4486.
44. Balciunaite, G., M. P. Keller, E. Balciunaite, L. Piali, S. Zuklys, Y. D. Mathieu, J. Gill, R. Boyd, D. J. Sussman, and G. A. Holländer. 2002. Wnt glycoproteins regulate the expression of FoxN1, the gene defective in nude mice. Nat. Immunol. 3: 1102-1108.
45. Zuklys, S., J. Gill, M. P. Keller, M. Hauri-Hohl, S. Zhanybekova, G. Balciunaite, K.-J. Na, L. T. Jeker, K. Hafen, N. Tsukamoto, et al. 2009. Stabilized b-catenin in thymic epithelial cells blocks thymus development and function. J. Immunol. 182: 2997-3007.
46. Heinonen, K. M., J. R. Vanegas, S. Brochu, J. Shan, S. J. Vainio, and C. Perreault. 2011. Wnt4 regulates thymic cellularity through the expansion of thymic epithelial cells and early thymic progenitors. Blood 118: 5163-5173.
47. Fang, X., S. X. Yu, Y. Lu, R. C. Bast, Jr., J. R. Woodgett, and G. B. Mills. 2000. Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A. Proc. Natl. Acad. Sci. USA 97: 11960-11965.
48. Liu, C., Y. Li, M. Semenov, C. Han, G. H. Baeg, Y. Tan, Z. Zhang, X. Lin, and X. He. 2002. Control of b-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108: 837-847.
49. White, A. J., W. E. Jenkinson, J. E. Cowan, S. M. Parnell, A. Bacon, N. D. Jones, E. J. Jenkinson, and G. Anderson. 2014. An essential role for medullary thymic epithelial cells during the intrathymic development of invariant NKT cells. J. Immunol. 192: 2659-2666.
50. Su, D. M., D. Aw, and D. B. Palmer. 2013. Immunosenescence: A product of the environment? Curr. Opin. Immunol. 25: 498-503.
51. Boehm, T., and J. B. Swann. 2013. Thymus involution and regeneration: two sides of the same coin? Nat. Rev. Immunol. 13: 831-838.
52. Holland, A. M., and M. R. van den Brink. 2009. Rejuvenation of the aging T cell compartment. Curr. Opin. Immunol. 21: 454-459.
53. Coder, B. D., H.Wang, L. Ruan, and D. M. Su. 2015. Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation. J. Immunol. 194: 5825-5837.
54. Zhang, X., X. R. Li, and J. Zhang. 2013. Current status and future perspectives of PI3K and mTOR inhibitor as anticancer drugs in breast cancer. Curr. Cancer Drug Targets 13: 175-187.