Browse > Article
http://dx.doi.org/10.4110/in.2012.12.5.207

T Cell Immunoglobulin Mucin Domain (TIM)-3 Promoter Activity in a Human Mast Cell Line  

Kim, Jung Sik (Department of Microbiology, Ajou University School of Medicine)
Shin, Dong-Chul (Department of Microbiology, Ajou University School of Medicine)
Woo, Min-Yeong (Department of Microbiology, Ajou University School of Medicine)
Kwon, Myung-Hee (Department of Microbiology, Ajou University School of Medicine)
Kim, Kyongmin (Department of Microbiology, Ajou University School of Medicine)
Park, Sun (Department of Microbiology, Ajou University School of Medicine)
Publication Information
IMMUNE NETWORK / v.12, no.5, 2012 , pp. 207-212 More about this Journal
Abstract
T cell immunoglobulin mucin domain (TIM)-3 is an immunomodulatory molecule and upregulated in T cells by several cytokines. TIM-3 also influences mast cell function but its transcriptional regulation in mast cells has not been clarified. Therefore, we examined the transcript level and the promoter activity of TIM-3 in mast cells. The TIM-3 transcript level was assessed by real-time RT-PCR and promoter activity by luciferase reporter assay. TIM-3 mRNA levels were increased in HMC-1, a human mast cell line by TGF-${\beta}1$ stimulation but not by stimulation with interferon (IFN)-${\alpha}$, IFN-${\lambda}$, TNF-${\alpha}$, or IL-10. TIM-3 promoter -349~+144 bp region relative to the transcription start site was crucial for the basal and TGF-${\beta}1$-induced TIM-3 promoter activities in HMC-1 cells. TIM-3 promoter activity was increased by over-expression of Smad2 and Smad4, downstream molecules of TGF-${\beta}1$ signaling. Our results localize TIM-3 promoter activity to the region spanning -349 to +144 bp in resting and TGF-${\beta}1$ stimulated mast cells.
Keywords
T cell immunoglobulin mucin domain-3; TGF-${\beta}1$; Transcription; Mast cells; Smad;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Sakuishi, K., P. Jayaraman, S. M. Behar, A. C. Anderson, and V. K. Kuchroo. 2011. Emerging Tim-3 functions in antimicrobial and tumor immunity. Trends Immunol. 32: 345-349
2 Sakuishi, K., L. Apetoh, J. M. Sullivan, B. R. Blazar, V. K. Kuchroo, and A. C. Anderson. 2010. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti- tumor immunity. J. Exp. Med. 207: 2187-2194.
3 Zhou, Q., M. E. Munger, R. G. Veenstra, B. J. Weigel, M. Hirashima, D. H. Munn, W. J. Murphy, M. Azuma, A. C. Anderson, V. K. Kuchroo, and B. R. Blazar. 2011. Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia. Blood 117: 4501-4510.
4 Lee, M. J., M. Y. Woo, Y. J. Chwae, M. H. Kwon, K. Kim, and S. Park. 2012. Down-regulation of interleukin-2 production by CD4(+) T cells expressing TIM-3 through suppression of NFAT dephosphorylation and AP-1 transcription. Immunobiology 217: 986-995.
5 Chiba, S., M. Baghdadi, H. Akiba, H. Yoshiyama, I. Kinoshita, H. Dosaka-Akita, Y. Fujioka, Y. Ohba, J. V. Gorman, J. D. Colgan, M. Hirashima, T. Uede, A. Takaoka, H. Yagita, and M. Jinushi. 2012. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat. Immunol. 13: 832-842.
6 Nakayama, M., H. Akiba, K. Takeda, Y. Kojima, M. Hashiguchi, M. Azuma, H. Yagita, and K. Okumura. 2009. Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation. Blood 113: 3821-3830.
7 Nakae, S., M. Iikura, H. Suto, H. Akiba, D. T. Umetsu, R. H. Dekruyff, H. Saito, and S. J. Galli. 2007. TIM-1 and TIM-3 enhancement of Th2 cytokine production by mast cells. Blood 110: 2565-2568.
8 Bischoff, S. C. 2007. Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data. Nat. Rev. Immunol. 7: 93-104.
9 Malaviya, R., T. Ikeda, E. Ross, and S. N. Abraham. 1996. Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha. Nature 381: 77-80.
10 Lee, D. M., D. S. Friend, M. F. Gurish, C. Benoist, D. Mathis, and M. B. Brenner. 2002. Mast cells: a cellular link between autoantibodies and inflammatory arthritis. Science 297: 1689-1692.
11 Lu, L. F., E. F. Lind, D. C. Gondek, K. A. Bennett, M. W. Gleeson, K. Pino-Lagos, Z. A. Scott, A. J. Coyle, J. L. Reed, J. Van Snick, T. B. Strom, X. X. Zheng, and R. J. Noelle. 2006. Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature 442: 997-1002.
12 Wiener, Z., B. Kohalmi, P. Pocza, J. Jeager, G. Tolgyesi, S. Toth, E. Gorbe, Z. Papp, and A. Falus. 2007. TIM-3 is expressed in melanoma cells and is upregulated in TGF-beta stimulated mast cells. J. Invest. Dermatol. 127: 906-914.
13 Broide, D. H., S. I. Wasserman, J. Alvaro-Gracia, N. J. Zvaifler, and G. S. Firestein. 1989. Transforming growth factor- beta 1 selectively inhibits IL-3-dependent mast cell proliferation without affecting mast cell function or differentiation. J. Immunol. 143: 1591-1597.
14 Schmierer, B. and C. S. Hill. 2007. TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility. Nat. Rev. Mol. Cell. Biol. 8: 970-982.
15 Conidi, A., S. Cazzola, K. Beets, K. Coddens, C. Collart, F. Cornelis, L. Cox, D. Joke, M. P. Dobreva, R. Dries, C. Esguerra, A. Francis, A. Ibrahimi, R. Kroes, F. Lesage, E. Maas, I. Moya, P. N. Pereira, E. Stappers, A. Stryjewska, V. van den Berghe, L. Vermeire, G. Verstappen, E. Seuntjens, L. Umans, A. Zwijsen, and D. Huylebroeck. 2011. Few Smad proteins and many Smad-interacting proteins yield multiple functions and action modes in $TGF\beta/BMP$ signaling in vivo. Cytokine Growth Factor Rev. 22: 287-300.
16 Soond, S. M. and A. Chantry. 2011. Selective targeting of activating and inhibitory Smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates$TGF\beta$signalling and EMT. Oncogene 30: 2451-2462.
17 Macey, M. R., J. L. Sturgill, J. K. Morales, Y. T. Falanga, J. Morales, S. K. Norton, N. Yerram, H. Shim, J. Fernando, A. M. Gifillan, G. Gomez, L. Schwartz, C. Oskeritzian, S. Spiegel, D. Conrad, and J. J. Ryan. 2010. IL-4 and TGF-beta 1 counterbalance one another while regulating mast cell homeostasis. J. Immunol. 184: 4688-4695.
18 Miller, H. R., S. H. Wright, P. A. Knight, and E. M. Thornton. 1999. A novel function for transforming growth factor-beta1: upregulation of the expression and the IgE-independent extracellular release of a mucosal mast cell granule-specific beta- chymase, mouse mast cell protease-1. Blood 93: 3473-3486.
19 Mortaz, E., M. E. Givi, C. A. Da Silva, G. Folkerts, and F. A. Redegeld. 2012. A relation between $TGF-\beta$ and mast cell tryptase in experimental emphysema models. Biochim. Biophys. Acta. 1822: 1154-1160.
20 Ganeshan, K. and P. J. Bryce. 2012. Regulatory T cells enhance mast cell production of IL-6 via surface-bound $TGF-\beta$. J. Immunol. 188: 594-603.
21 Anderson, A. C., G. M. Lord, V. Dardalhon, D. H. Lee, C. A. Sabatos-Peyton, L. H. Glimcher, and V. K. Kuchroo. 2010. T-bet, a Th1 transcription factor regulates the expression of Tim-3. Eur. J. Immunol. 40: 859-866.
22 Yoon, S. J., M. J. Lee, D. C. Shin, J. S. Kim, Y. J. Chwae, M. H. Kwon, K. Kim, and S. Park. 2011. Activation of mitogen activated protein kinase-Erk kinase (MEK) increases T cell immunoglobulin mucin domain-3 (TIM-3) transcription in human T lymphocytes and a human mast cell line. Mol. Immunol. 48: 1778-1783.
23 Zhang, J., D. Daley, L. Akhabir, D. Stefanowicz, M. Chan-Yeung, A. B. Becker, C. Laprise, P. D. Paré, and A. J. Sandford. 2009. Lack of association of TIM3 polymorphisms and allergic phenotypes. BMC Med. Genet. 10: 62.