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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 繆希椿(Shi-Chuen Miaw) | |
| dc.contributor.author | Yu-Hsien Lin | en |
| dc.contributor.author | 林育仙 | zh_TW |
| dc.date.accessioned | 2021-05-15T17:50:55Z | - |
| dc.date.available | 2019-10-09 | |
| dc.date.available | 2021-05-15T17:50:55Z | - |
| dc.date.copyright | 2014-10-09 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-08-18 | |
| dc.identifier.citation | Bauquet, A.T., Jin, H., Paterson, A.M., Mitsdoerffer, M., Ho, I.C., Sharpe, A.H., and Kuchroo, V.K. (2009). The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells. Nat. Immunol. 10, 167-175.
Benkhelifa, S., Provot, S., Nabais, E., Eychene, A., Calothy, G., and Felder-Schmittbuhl, M.P. (2001). Phosphorylation of MafA is essential for its transcriptional and biological properties. Mol. Cell Biol. 21, 4441-4452. Blonska, M., Joo, D., Nurieva, R.I., Zhao, X., Chiao, P., Sun, S.C., Dong, C., and Lin, X. (2013). Activation of the transcription factor c-Maf in T cells is dependent on the CARMA1-IKKbeta signaling cascade. Sci Signal 6, ra110. Cao, S., Liu, J., Song, L., and Ma, X. (2005). The protooncogene c-Maf is an essential transcription factor for IL-10 gene expression in macrophages. J. Immunol. 174, 3484-3492. Eychene, A., Rocques, N., and Pouponnot, C. (2008). A new MAFia in cancer. Nature reviews. Cancer 8, 683-693. Gomez-Rodriguez, J., Wohlfert, E.A., Handon, R., Meylan, F., Wu, J.Z., Anderson, S.M., Kirby, M.R., Belkaid, Y., and Schwartzberg, P.L. (2014). Itk-mediated integration of T cell receptor and cytokine signaling regulates the balance between Th17 and regulatory T cells. J Exp Med 211, 529-543. Graham, L.G., Ben-Sasson, S.Z., Seder, R., Finkelman, F.D., and Paul, W.E. (1990). Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med 172, 921-929. Guo, L., Hu-Li, J., and Paul, W.E. (2004). Probabilistic regulation of IL-4 production in Th2 cells: accessibility at the Il4 locus. Immunity 20, 193-203. Harrington, L.E., Hatton, R.D., Mangan, P.R., Turner, H., Murphy, T.L., Murphy, K.M., and Weaver, C.T. (2005). Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat. Immunol. 6, 1123-1132. Herath, N.I., Rocques, N., Garancher, A., Eychene, A., and Pouponnot, C. (2014). GSK3-mediated MAF phosphorylation in multiple myeloma as a potential therapeutic target. Blood Cancer J 4, e175. Hiramatsu, Y., Suto, A., Kashiwakuma, D., Kanari, H., Kagami, S., Ikeda, K., Hirose, K., Watanabe, N., Grusby, M.J., Iwamoto, I., and Nakajima, H. (2010). c-Maf activates the promoter and enhancer of the IL-21 gene, and TGF-beta inhibits c-Maf-induced IL-21 production in CD4+ T cells. J. Leukoc. Biol. 87, 703-712. Ho, I.C., and Glimcher, L.H. (2002). Transcription: tantalizing times for T cells. Cell. 109, 109-120. Hwang, E.S., Szabo, S.J., Schwartzberg, P.L., and Glimcher, L.H. (2005). T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science (New York, N.Y.) 307, 430-433. Jin, W., and Dong, C. (2013). IL-17 cytokines in immunity and inflammation. Emerging Microbes & Infections 2, e60. Kawauchi, S., Takahashi, S., Nakajima, O., Ogino, H., Morita, M., Nishizawa, M., Yasuda, K., and Yamamoto, M. (1999). Regulation of Lens Fiber Cell Differentiation by Transcription Factor c-Maf. Journal of Biological Chemistry 274, 19254-19260. Kim, J.I., Ho, I.C., Grusby, M.J., and Glimcher, L.H. (1999). The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines. Immunity 10. Korn, T., Bettelli, E., Oukka, M., and Kuchroo, V.K. (2009). IL-17 and Th17 Cells. Annual review of immunology 27, 485-517. Kurokawa, H., Motohashi, H., Sueno, S., Kimura, M., Takagawa, H., Kanno, Y., Yamamoto, M., and Tanaka, T. (2009). Structural basis of alternative DNA recognition by Maf transcription factors. Molecular and cellular biology 29, 6232-6244. Lai, C.Y., Lin, S.Y., Wu, C.K., Yeh, L.T., Sytwu, H.K., and Miaw, S.C. (2012). Tyrosine phosphorylation of c-Maf enhances the expression of IL-4 gene. Journal of immunology 189, 1545-1550. Lin, B.S., Tsai, P.Y., Hsieh, W.Y., Tsao, H.W., Liu, M.W., Grenningloh, R., Wang, L.F., Ho, I.C., and Miaw, S.C. (2010). SUMOylation attenuates c-Maf-dependent IL-4 expression. Eur. J. Immunol. 40, 1174-1184. Luzina, I.G., Keegan, A.D., Heller, N.M., Rook, G.A., Shea-Donohue, T., and Atamas, S.P. (2012). Regulation of inflammation by interleukin-4: a review of 'alternatives'. J. Leukoc. Biol.y 92, 753-764. M., B., Sefton., and Campbell., M.-A. (1991). The Role of Tyrosine Protein Phosphorylation in Lymphocyte Activation. Annu Rev Cell Biol 7, 257-274. Moriguchi, T., Hamada, M., Morito, N., Terunuma, T., Hasegawa, K., Zhang, C., Yokomizo, T., Esaki, R., Kuroda, E., Yoh, K., et al. (2006). MafB is essential for renal development and F4/80 expression in macrophages. Mol. Cell Biol. 26, 5715-5727. Mosmann, T.R., Cherwinski, H., Bond, M.W., Giedlin, M.A., and Coffman, R.L. (1986). Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136, 2348-2357. Mosmann, T.R., and Coffman, R.L. (1989). TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol. 7, 145-173. Nolen, B., Taylor, S., and Ghosh, G. (2004). Regulation of protein kinases; controlling activity through activation segment conformation. Mol. Cell 15, 661-675. Park, H., Li, Z., Yang, X.O., Chang, S.H., Nurieva, R., Wang, Y.H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., and Dong, C. (2005). A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 6, 1133-1141. Pot, C., Jin, H., Awasthi, A., Liu, S.M., Lai, C.Y., Madan, R., Sharpe, A.H., Karp, C.L., Miaw, S.C., Ho, I.C., and Kuchroo, V.K. (2009). Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells. J. Immunol. 183, 797-801. Renate, A.M., Lucia, G., LuizV, P.i., Nancy, N.-T., Ralf, K., Klaus, R., Werner, M., Mark, D., Fred, F., Robert, L.C., and Herbert, C.M. (1996). Interleukin (IL)-4-independent immunoglobulin class switch to immunoglobulin (Ig)E in the mouse. J Exp Med 184, 1651-1661. Rocques, N., Abou Zeid, N., Sii-Felice, K., Lecoin, L., Felder-Schmittbuhl, M.P., Eychene, A., and Pouponnot, C. (2007). GSK-3-mediated phosphorylation enhances Maf-transforming activity. Mol. Cell 28, 584-597. Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., and Toda, M. (1995). Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155, 1151-1164. Schaerli., P., Willimann., K., Lang., A.B., Lipp., M., Pius Loetscher, and Moser., B. (2000). CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med 192, 1553-1562. Schwartzberg, P.L., Finkelstein, L.D., and Readinger, J.A. (2005). TEC-family kinases: regulators of T-helper-cell differentiation. Nat. Rev. Immunol. 5, 284-295. Sii-Felice, K., Pouponnot, C., Gillet, S., Lecoin, L., Girault, J.A., Eychene, A., and Felder-Schmittbuhl, M.P. (2005). MafA transcription factor is phosphorylated by p38 MAP kinase. FEBS Lett. 579, 3547-3554. Smith-Garvin, J.E., Koretzky, G.A., and Jordan, M.S. (2009). T Cell Activation. Annu. Rev. Immunol.27, 591-619. Spolski, R., and Leonard, W.J. (2008). Interleukin-21: basic biology and implications for cancer and autoimmunity. Annu. Rev. Immunol. 26, 57-79. Tillmanns, S., Otto, C., Jaffray, E., Du Roure, C., Bakri, Y., Vanhille, L., Sarrazin, S., Hay, R.T., and Sieweke, M.H. (2007). SUMO modification regulates MafB-driven macrophage differentiation by enabling Myb-dependent transcriptional repression. Mol. Cell Biol. 27, 5554-5564. Ubersax, J.A., and Ferrell, J.E., Jr. (2007). Mechanisms of specificity in protein phosphorylation. Nat. Rev. Mol. Cell Biol. 8, 530-541. Wei, L., Laurence, A., Elias, K., and O'Shea, J. (2007). IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner. J Biol Chem 282, 34605-34610. Xu, J., Yang, Y., Qiu, G., Lal, G., Wu, Z., Levy, D.E., Ochando, J.C., Bromberg, J.S., and Ding, Y. (2009). c-Maf regulates IL-10 expression during Th17 polarization. J. immunol. 182, 6226-6236. Yang, Y., Ochando, J., Yopp, A., Bromberg, J.S., and Ding, Y. (2005). IL-6 Plays a Unique Role in Initiating c-Maf Expression during Early Stage of CD4 T Cell Activation. J. immunol. 174, 2720-2729. Yoshida, T., Ohkumo, T., Ishibashi, S., and Yasuda, K. (2005). The 5'-AT-rich half-site of Maf recognition element: a functional target for bZIP transcription factor Maf. Nucleic Acids Res. 33, 3465-3478. Zhang, C., Moriguchi, T., Kajihara, M., Esaki, R., Harada, A., Shimohata, H., Oishi, H., Hamada, M., Morito, N., Hasegawa, K., et al. (2005). MafA is a key regulator of glucose-stimulated insulin secretion. Mol. Cell Biol. 25, 4969-4976. Zhou, L., Chong, M.M., and Littman, D.R. (2009). Plasticity of CD4+ T cell lineage differentiation. Immunity 30, 646-655. Zhu, J., and Paul, W.E. (2008). CD4 T cells: fates, functions, and faults. Blood 112, 1557-1569. Zhu, J., Yamane, H., and Paul, W.E. (2010). Differentiation of effector CD4 T cell populations. Annu. Rev. Immunol. 28, 445-489. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/5009 | - |
| dc.description.abstract | Maf家族的蛋白質，參與了細胞當中各種不同的生物反應與機制，包括水晶體的發育，免疫細胞的分化以及腫瘤的形成。c-Maf是large Maf家族成員的一員，在免疫系統中扮演著多樣且十分重要的角色。c-Maf被發現可以在第二型輔助性T細胞中轉錄活化介白素四的表現，也可在第十七型輔助性T細胞中轉錄活化介白素二十一的表現。在我們之前的研究當中發現，c-Maf在第21,92,131號酪胺酸的位置可以被磷酸化。而且在這三個位置的磷酸化有助於c-Maf結合到介白素四的啟動子，也可促進第二型輔助性T細胞分泌介白素四。在本篇當中，為了進一步了解c-Maf 在第十七型輔助性T細胞中，對介白素二十一的調控。我們首先確認了c-Maf可以在第十七型輔助性T細胞中被磷酸化。接著我們將野生型c-Maf(WT c-Maf)和磷酸化位置被突變的c-Maf(Y3F c-MAf)過度表現在第十七型輔助性T細胞。發現介白素二十一的表現在Y3F c-Maf當中有下降的趨勢。我們也同時使用染色質免疫沉澱分析，發現相較於WT c-Maf，Y3F c-Maf結合到介白素二十一的啟動子的能力較差。總結來說，我們發現c-Maf的磷酸化會影響c-Maf結合到啟動子的能力，進而也影響到對介白素轉錄活化的能力。 | zh_TW |
| dc.description.abstract | Maf (Musculoaponeurotic fibrosarcoma) proteins are involved in a variety of biological processes such as oncogenesis, lens development and differentiation. c-Maf, one of the large Maf proteins, plays important roles in immune system. c-Maf is the specific transcription factor of the IL-4 and IL-21 genes in type 2 helper T cell (Th2) and type 17 helper T cell (Th17), respectively. In our previous study, we found that c-Maf undergoes phosphorylation, a post-translational modification, in Th2 cells. The Tyrosine 21, 92, and 131 residues are identified as sites for tyrosine phosphorylation in c-Maf. We previously reported that the tyrosine-phosphorylation of c-Maf enhances its transactivity on IL-4 gene expression in Th2 cells. To understand the regulation of IL-21 cytokine gene expression by tyrosine-phosphorylation of c-Maf in Th17 cells, we showed c-Maf is subjected to tyrosine-phosphorylation in Th17 cells. We introduced WT c-Maf or c-Maf mutant carrying deficiency in tyrosine-phosphorylation (Y3F) into primary murine Th17 cells via retrovirus transduction and measured the gene expression of IL-21 with quantitive PCR and ELISA assay. We demonstrated that IL-21 production is reduced by c-Maf Y3F. Importantly, We performed chromatin immunoprecipitation to analyzed the binding ability of WT c-Maf or c-Maf Y3F to IL-21 promoter and found that c-Maf Y3F binds relatively weakly to IL-21 promoter compared to WT c-Maf. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-15T17:50:55Z (GMT). No. of bitstreams: 1 ntu-103-R01449008-1.pdf: 1565053 bytes, checksum: b6d9e4bb5a6a031b96e928284a780eba (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | Acknowledgement i
中文摘要 iii Abstract iv Chapter I Introduction 1 1.1 Helper T cell differentiation 2 1.2 Overview of Maf family 4 1.3 The function of c-Maf in immune system 5 1.5 Post-translational modification of c-Maf 8 1.6 Rationale 9 Chapter II Materials and Methods 10 1. Materials 11 1-1 Buffers 11 1-2 Antibodies and cytokines 14 1-3 Primers 15 2. Experimental procedures 16 2-1 Mice 16 2-2 Generation of the reconstituted c-Maf deficiency mice 16 2-3 Purification and differentiation of Th cells 16 2-4 Retrovirus Preparation from HEK293T cells. 17 2-5 Retroviral transduction 18 2-6 ChIP assay 19 2-7 Western Blotting 20 2-8 Immunoprecipitation and Immunoblot Analyses 21 2-9 ELISA assay 22 Chapter III Result 23 3.1 Endogenous c-Maf undergoes Tyrosine Phosphorylation in both Th2 and Th17 cells. 24 3.2 IL-21 production was impaired in Th17 cell transduced with tyrosine phosphorylation deficient c-Maf. 25 3.3 Tyrosine phosphorylation of c-Maf enhances c-Maf recruitment to IL-4 and IL-21 promoter in Th2 and Th17 cells respectively. 26 Chapter IV Discussion 29 Tyrosine phosphorylation plays a significant role in regulating c-Maf transactivity. 30 Chapter V Figures 32 Figure 1. Endogenous c-Maf undergoes Tyrosine Phosphorylation in both Th2 and Th17 cells. 34 Figure 2. Experimental design and constructs 35 Figure 3. The retroviral transduction efficiency of primary CD4+ T cells was determined by flow cytometry. 36 Figure 4. Mutation of c-Maf in Phosphorylation site suppresses Il21 expression, but not Il17, in WT Th17 cells 37 Figure 5. Mutation of c-Maf in Phosphorylation site suppresses IL-21 production, but not IL-17 in c-Maf KO Th17 cells 38 Figure 6. The recruitment of WT and Y3F mutant of c-Maf to IL-4 promoter in WT Th2 cells. 40 Figure 7. The recruitments of endogenous c-Maf to IL-21 promoter in Th17 cells 41 Figure 8. The recruitment of WT and Y3F mutant of c-MAf to IL-21 promoter in WT Th17 cells. 42 Figure 9. The recruitment of WT and Y3F mutant of c-Maf to IL-21 promoter in WT Th17 cells. 43 Supplementary 44 Supplementary Figure. c-Maf KO bone marrow chimeric mice. 44 Chapter VI References 45 | |
| dc.language.iso | en | |
| dc.subject | 輔助型T細胞 | zh_TW |
| dc.subject | 介白素二十一 | zh_TW |
| dc.subject | 介白素四 | zh_TW |
| dc.subject | IL-21 | en |
| dc.subject | Th2 | en |
| dc.subject | IL-4 | en |
| dc.subject | Th17 | en |
| dc.subject | c-Maf | en |
| dc.title | 探討在輔助型T細胞中酪胺酸磷酸化之c-Maf對於介白素四與二十一啟動子的結合機轉 | zh_TW |
| dc.title | Recruitment of tyrosine-phosphorylated c-Maf to Il4 and Il21 promoters in helper T cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 伍安怡(Betty Wu-Hsieh),顧家綺(Chia-Chi Ku) | |
| dc.subject.keyword | 輔助型T細胞,介白素四,介白素二十一, | zh_TW |
| dc.subject.keyword | c-Maf,Th2,Th17,IL-4,IL-21, | en |
| dc.relation.page | 52 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2014-08-19 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
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