Phosphatase Wip1 is essential for the maturation and homeostasis of medullary thymic epithelial cells in mice

Journal of Immunology

Volumn 191, Issue 6, 2013, Pages 3210-3220

  Zhang, Lianfeng ^b   Sun, Lina ^a   Li, Hongran ^a   Luo, Haiying ^a   Zhang, Lianjun ^a   Hu, Xuelian ^a   Yang, Tao ^a   Sun, Chenming ^a   Chen, Hui ^a   Zhao, Yong ^a  

^a INSTITUTE OF ZOOLOGY   (China)

^b PEKING UNION MEDICAL COLLEGE   (China)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOIMMUNE REGULATOR PROTEIN; B7 ANTIGEN; CD40 ANTIGEN; CD40 LIGAND; EPITHELIAL CELL ADHESION MOLECULE; INVOLUCRIN; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; MITOGEN ACTIVATED PROTEIN KINASE P38; P53 INDUCED PHOSPHATASE 1; PHOSPHATASE; PLANT LECTIN; PROTEIN BP 1; TISSUE ANTIGEN; UNCLASSIFIED DRUG;

ADULT ANIMAL; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIGEN EXPRESSION; ARTICLE; BONE MARROW CELL; CELL COUNT; CELL DAMAGE; CELL DIFFERENTIATION; CELL MATURATION; CONTROLLED STUDY; CULTURE TECHNIQUE; DISEASE SEVERITY; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME DEFICIENCY; EPITHELIUM CELL; FETUS; FETUS DEVELOPMENT; HOMEOSTASIS; IMMUNOREGULATION; IRRADIATION; KNOCKOUT MOUSE; LETHALITY; MEDULLARY THYMIC EPITHELIAL CELL; MOUSE; NONHUMAN; ORGAN CULTURE; POSTNATAL DEVELOPMENT; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; T LYMPHOCYTE; THYMOCYTE; TISSUE REGENERATION; ULEX EUROPAEUS;

ANIMALS; CELL DIFFERENTIATION; CELL SEPARATION; EPITHELIAL CELLS; FEMALE; FLOW CYTOMETRY; FLUORESCENT ANTIBODY TECHNIQUE; HOMEOSTASIS; IMMUNOHISTOCHEMISTRY; MALE; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; PHOSPHOPROTEIN PHOSPHATASES; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; STROMAL CELLS; THYMUS GLAND;

EID: 84884273176     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1300363     Document Type: Article

References (45)

1. Anderson, G., and Y. Takahama. 2012. Thymic epithelial cells: working class heroes for T cell development and repertoire selection. Trends Immunol. 33: 256-263.
2. Manley, N. R., and B. G. Condie. 2010. Transcriptional regulation of thymus organogenesis and thymic epithelial cell differentiation. Prog. Mol. Biol. Transl. Sci. 92: 103-120.
3. Bleul, C. C., T. Corbeaux, A. Reuter, P. Fisch, J. S. Mönting, and T. Boehm. 2006. Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. Nature 441: 992-996.
4. Rossi, S. W., W. E. Jenkinson, G. Anderson, and E. J. Jenkinson. 2006. Clonal analysis reveals a common progenitor for thymic cortical and medullary epithelium. Nature 441: 988-991.
5. Blackburn, C. C., C. L. Augustine, R. Li, R. P. Harvey, M. A. Malin, R. L. Boyd, J. F. Miller, and G. Morahan. 1996. The nu gene acts cell-autonomously and is required for differentiation of thymic epithelial progenitors. Proc. Natl. Acad. Sci. USA 93: 5742-5746.
6. Sun, L., H. Luo, H. Li, and Y. Zhao. 2013. Thymic epithelial cell development and differentiation: cellular and molecular regulation. Protein Cell 4: 342-355.
7. Akiyama, T., Y. Shimo, H. Yanai, J. Qin, D. Ohshima, Y. Maruyama, Y. Asaumi, J. Kitazawa, H. Takayanagi, J. M. Penninger, 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.
8. Alexandropoulos, K., and N. M. Danzl. 2012. Thymic epithelial cells: antigen presenting cells that regulate T cell repertoire and tolerance development. Immunol. Res. 54: 177-190.
9. Roberts, N. A., A. J. White, W. E. Jenkinson, G. Turchinovich, K. Nakamura, D. R. Withers, F. M. McConnell, G. E. Desanti, C. Benezech, S. M. Parnell, et al. 2012. Rank signaling links the development of invariant gd T cell progenitors and Aire+ medullary epithelium. Immunity 36: 427-437.
10. Martins, V. C., T. Boehm, and C. C. Bleul. 2008. Ltbetar signaling does not regulate Aire-dependent transcripts in medullary thymic epithelial cells. J. Immunol. 181: 400-407.
11. Fiscella, M., H. Zhang, S. Fan, K. Sakaguchi, S. Shen, W. E. Mercer, G. F. Vande Woude, P. M. O'Connor, and E. Appella. 1997. Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner. Proc. Natl. Acad. Sci. USA 94: 6048-6053.
12. Le Guezennec, X., and D. V. Bulavin. 2010. WIP1 phosphatase at the crossroads of cancer and aging. Trends Biochem. Sci. 35: 109-114.
13. Salminen, A., and K. Kaarniranta. 2011. Control of p53 and NF-kB signaling by WIP1 and MIF: role in cellular senescence and organismal aging. Cell. Signal. 23: 747-752.
14. Lu, X., T. A. Nguyen, S. H. Moon, Y. Darlington, M. Sommer, and L. A. Donehower. 2008. The type 2C phosphatase Wip1: an oncogenic regulator of tumor suppressor and DNA damage response pathways. Cancer Metastasis Rev. 27: 123-135.
15. Chew, J., S. Biswas, S. Shreeram, M. Humaidi, E. T. Wong, M. K. Dhillion, H. Teo, A. Hazra, C. C. Fang, E. López-Collazo, et al. 2009. WIP1 phosphatase is a negative regulator of NF-kB signalling. Nat. Cell Biol. 11: 659-666.
16. Bulavin, D. V., C. Phillips, B. Nannenga, O. Timofeev, L. A. Donehower, C. W. Anderson, E. Appella, and A. J. Fornace, Jr. 2004. Inactivation of theWip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16Ink4a-p19Arf pathway. Nat. Genet. 36: 343-350.
17. Oliva-Trastoy, M., V. Berthonaud, A. Chevalier, C. Ducrot, M. C. Marsolier-Kergoat, C. Mann, and F. Leteurtre. 2007. The Wip1 phosphatase (PPM1D) antagonizes activation of the Chk2 tumour suppressor kinase. Oncogene 26: 1449-1458.
18. Schito, M. L., O. N. Demidov, S. Saito, J. D. Ashwell, and E. Appella. 2006. Wip1 phosphatase-deficient mice exhibit defective T cell maturation due to sustained p53 activation. J. Immunol. 176: 4818-4825.
19. Choi, J., B. Nannenga, O. N. Demidov, D. V. Bulavin, A. Cooney, C. Brayton, Y. Zhang, I. N. Mbawuike, A. Bradley, E. Appella, and L. A. Donehower. 2002. Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control. Mol. Cell. Biol. 22: 1094-1105.
20. Liu, G., X. Hu, B. Sun, T. Yang, J. Shi, L. Zhang, and Y. Zhao. 2013. Phosphatase Wip1 negatively regulates neutrophil development through p38 MAPKSTAT1. Blood 121: 519-529.
21. 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.
22. Liu, G., S. Burns, G. Huang, K. Boyd, R. L. Proia, R. A. Flavell, and H. Chi. 2009. The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR. Nat. Immunol. 10: 769-777.
23. Liu, G., K. Duan, H. Ma, Z. Niu, J. Peng, and Y. Zhao. 2011. An instructive role of donor macrophages in mixed chimeras in the induction of recipient CD4+ Foxp3+ Treg cells. Immunol. Cell Biol. 89: 827-835.
24. Duan, K., B. Zhang, W. Zhang, Y. Zhao, Y. Qu, C. Sun, and Y. Zhao. 2011. Efficient peripheral construction of functional human regulatory CD4+CD25high Foxp3+ T cells in NOD/SCID mice grafted with fetal human thymus/liver tissues and CD34+ cells. Transpl. Immunol. 25: 173-179.
25. Farr, A. G., and S. K. Anderson. 1985. Epithelial heterogeneity in the murine thymus: fucose-specific lectins bind medullary epithelial cells. J. Immunol. 134: 2971-2977.
26. Tykocinski, L. O., A. Sinemus, and B. Kyewski. 2008. The thymus medulla slowly yields its secrets. Ann. N. Y. Acad. Sci. 1143: 105-122.
27. Zhang, L., L. Sun, and Y. Zhao. 2007. Thymic epithelial progenitor cells and thymus regeneration: an update. Cell Res. 17: 50-55.
28. Gillard, G. O., and A. G. Farr. 2006. Features of medullary thymic epithelium implicate postnatal development in maintaining epithelial heterogeneity and tissue-restricted antigen expression. J. Immunol. 176: 5815-5824.
29. Galy, A. H., and H. Spits. 1992. CD40 is functionally expressed on human thymic epithelial cells. J. Immunol. 149: 775-782.
30. Nishikawa, Y., F. Hirota, M. Yano, H. Kitajima, J. Miyazaki, H. Kawamoto, Y. Mouri, and M. Matsumoto. 2010. Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation. J. Exp. Med. 207: 963-971.
31. Yano, M., N. Kuroda, H. Han, M. Meguro-Horike, Y. Nishikawa, H. Kiyonari, K. Maemura, Y. Yanagawa, K. Obata, S. Takahashi, et al. 2008. Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance. J. Exp. Med. 205: 2827-2838.
32. Yi, H., Y. Zhen, L. Jiang, J. Zheng, and Y. Zhao. 2006. The phenotypic characterization of naturally occurring regulatory CD4+CD25+ T cells. Cell. Mol. Immunol. 3: 189-195.
33. Zheng, Q., Y. Xu, Y. Liu, B. Zhang, X. Li, F. Guo, and Y. Zhao. 2009. Induction of Foxp3 demethylation increases regulatory CD4+CD25+ T cells and prevents the occurrence of diabetes in mice. J. Mol. Med. 87: 1191-1205.
34. Gray, D. H., N. Seach, T. Ueno, M. K. Milton, A. Liston, A. M. Lew, C. C. Goodnow, and R. L. Boyd. 2006. Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells. Blood 108: 3777-3785.
35. Gäbler, J., J. Arnold, and B. Kyewski. 2007. Promiscuous gene expression and the developmental dynamics of medullary thymic epithelial cells. Eur. J. Immunol. 37: 3363-3372.
36. Rossi, S. W., M. Y. Kim, A. Leibbrandt, S. M. Parnell, W. E. Jenkinson, S. H. Glanville, F. M. McConnell, H. S. Scott, J. M. Penninger, E. J. Jenkinson, et al. 2007. RANK signals from CD4+32 inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla. J. Exp. Med. 204: 1267-1272.
37. Hikosaka, Y., T. Nitta, I. Ohigashi, K. Yano, N. Ishimaru, Y. Hayashi, M. Matsumoto, K. Matsuo, J. M. Penninger, H. Takayanagi, et al. 2008. The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. Immunity 29: 438-450.
38. Boehm, T., S. Scheu, K. Pfeffer, and C. C. Bleul. 2003. Thymic medullary epithelial cell differentiation, thymocyte emigration, and the control of autoimmunity require lympho-epithelial cross talk via LTbR. J. Exp. Med. 198: 757-769.
39. Revest, J. M., R. K. Suniara, K. Kerr, J. J. Owen, and C. Dickson. 2001. Development of the thymus requires signaling through the fibroblast growth factor receptor R2-IIIb. J. Immunol. 167: 1954-1961.
40. 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.
41. Desanti, G. E., J. E. Cowan, S. Baik, S. M. Parnell, A. J. White, J. M. Penninger, P. J. Lane, E. J. Jenkinson, W. E. Jenkinson, and G. Anderson. 2012. Developmentally regulated availability of RANKL and CD40 ligand reveals distinct mechanisms of fetal and adult cross-talk in the thymus medulla. J. Immunol. 189: 5519-5526.
42. Takekawa, M., M. Adachi, A. Nakahata, I. Nakayama, F. Itoh, H. Tsukuda, Y. Taya, and K. Imai. 2000. p53-Inducible Wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation. EMBO J. 19: 6517-6526.
43. Lu, X., O. Ma, T. A. Nguyen, S. N. Jones, M. Oren, and L. A. Donehower. 2007. The Wip1 phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop. Cancer Cell 12: 342-354.
44. Akiyama, T., S. Maeda, S. Yamane, K. Ogino, M. Kasai, F. Kajiura, M. Matsumoto, and J. Inoue. 2005. Dependence of self-tolerance on TRAF6-directed development of thymic stroma. Science 308: 248-251.
45. Dunn, R. J., C. J. Luedecker, H. S. Haugen, C. H. Clegg, and A. G. Farr. 1997. Thymic overexpression of CD40 ligand disrupts normal thymic epithelial organization. J. Histochem. Cytochem. 45: 129-141.