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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李建國(Chien-Kuo Lee) | |
| dc.contributor.author | Yi-Ling Chen | en |
| dc.contributor.author | 陳怡伶 | zh_TW |
| dc.date.accessioned | 2021-06-14T17:11:37Z | - |
| dc.date.available | 2016-10-05 | |
| dc.date.copyright | 2011-10-05 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-12 | |
| dc.identifier.citation | 1. Vremec D, Pooley J, Hochrein H, Wu L, Shortman K. CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and spleen. Journal of Immunology 2000.
2. Anjuère F, Martin P, Ferrero I, Fraga ML, Hoyo GMd. Definition of dendritic cell subpopulations present in the spleen, peyer's patched, lymph Nodes. Blood 1999. 3. Thibaut De Smedt, Bernard Pajak, Eric Muraille, Laurence Lespagnard, Ernst Heinen, Patrick De Baetselier, et al. Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo. J Exp Med 1996. 4. Caetano Reis e Sousa, Sara Hieny, Tanya Scharton-Kersten, Dragana Jankovic, Hugues Charest, Ronald N. Germain, et al. In vivo microbial stimulation induces Rapid CD40 Ligand-independent Production of Interleukin 12 by Dendritic Cells and their Redistribution to T Cell J Exp Med 1997. 5. Alexander D. Edwards, Damien Chaussabel, Tomlinson, Oliver Schulz, Alan Sher, Sousa CRe. Relationships among murine CD11c(high) dendritic cell subsets as revealed by baseline gene expression patterns. Journal of Immunology 2003. 6. Hubertus Hochrein, Ken Shortman, David Vremec, Bernadette Scott, Hertzog P, O’Keeffe M. Differential production of IL-12, IFN-alpha, and IFN-gamma by mouse dendritic cell subsets. Journal of Immunology 2001. 7. Roberto Maldonado-López, Thibaut De Smedt, Patrick Michel, Jacques Godfroid, Bernard Pajak, Carlo Heirman, et al. CD8alpha+ and CD8alpha- subclasses of dendritic cells direct the development of distinct T helper cells in vivo. J Exp Med 1999. 8. B. PULENDRAN, J. L. SMITH GC, K. BRASEL, D. PETTIT, E.MARASKOVSKY, MALISZEWSKI CR. Distinct dendritic cell subsets differentially regulate the class of immune response invivo. Proc Natl Acad Sci U S A 1999. 9. Reizis B, Bunin A, Ghosh HS, Lewis KL, Sisirak V. Plasmacytoid Dendritic Cells: Recent Progress and Open Questions. Annual Review of Immunology 2011,29:163-183. 10. Asselin-Paturel C, Boonstra A, Dalod M, Durand I, Yessaad N, Dezutter-Dambuyant C, et al. Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nature Immunology 2001,2:1144-1150. 11. Asselin-Paturel C, Trinchieri G. Production of type I interferons: plasmacytoid dendritic cells and beyond. Journal of Experimental Medicine 2005,202:461-465. 12. Marc Dalod, Thais P. Salazar-Mather, Lene Malmgaard, Casey Lewis, Carine Asselin-Paturel, Francine Brière, et al. Interferon α/β and Interleukin 12 Responses to Viral Infections_pathways regulating dendritic cell cytokine expression in vivo. J Exp Med 2002. 13. Kawai T, Sato S, Ishii KJ, Coban C, Hemmi H, Yamamoto M, et al. Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat Immunol 2004,5:1061-1068. 14. Kenya Honda, Yusuke Ohba, Hideyuki Yanai, Hideo Negishi, Tatsuaki Mizutani, Akinori Takaoka, et al. Spatiotemporal regulation of MyD88-IRF-7signalling for robust type-I interferon induction. Nature 2005,434:1031-1035. 15. Tailor P, Tamura T, Kong HJ, Kubota T, Kubota M, Borghi P, et al. The feedback phase of type I interferon induction in dendritic cells requires interferon regulatory factor 8. Immunity 2007,27:228-239. 16. Krug A, French AR, Barchet W, Fischer JAA, Dzionek A, Pingel JT, et al. TLR9-Dependent Recognition of MCMV by IPC and DC Generates Coordinated Cytokine Responses that Activate Antiviral NK Cell Function. Immunity 2004,21:107-119. 17. Sapoznikov A, Fischer JAA, Zaft T, Krauthgamer R, Dzionek A, Jung S. Organ-dependent in vivo priming of naive CD4+,but not CD8+,T cells by plasmacytoid dendritic cells. Journal of Experimental Medicine 2007,204:1923-1933. 18. Marina Cella, Fabio Facchetti, Antonio Lanzavecchia, Colonna M. Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent TH1 polarization. Nature 2000. 19. Boonstra A, Asselin-Paturel C, Gilliet M, Crain C, Trinchieri G, Liu YJ, et al. Flexibility of Mouse Classical and Plasmacytoid-derived Dendritic Cells in Directing T Helper Type 1 and 2 Cell Development: Dependency on Antigen Dose and Differential Toll-like Receptor Ligation. Journal of Experimental Medicine 2002,197:101-109. 20. Salio M. CpG-matured Murine Plasmacytoid Dendritic Cells Are Capable of In Vivo Priming of Functional CD8 T Cell Responses to Endogenous but Not Exogenous Antigens. Journal of Experimental Medicine 2004,199:567-579. 21. Zhang J, Raper A, Sugita N, Hingorani R, Salio M, Palmowski MJ, et al. Characterisation of Siglec-H as a novel endocyticreceptor expressed on murine plasmacytoid dendritic cell precursors. Blood 2006. 22. Amanda L. Blasius, Emanuele Giurisato, Marina Cella, Robert D. Schreiber, Shaw AS, Colonna M. BST2 is a specific marker of type I IFN producing cells in naive mouse but a promiscuous cell surface antigen followig IFN stimulation. Journal of Immunology 2006. 23. Carine Asselin-Paturel, Géraldine Brizard, Jean-Jacques Pin, Francine Brière, Trinchieri. G. Mouse Strain Differences in Plasmacytoid Dendritic Cell Frequency and Function Revealed by a Novel Monoclonal Antibody. Journal of Immunology 2003. 24. Noriko Toyama-Sorimachi, Yoshiki Omatsu, Onoda A, Yusuke Tsujimura, Tomonori Iyoda, Akiko Kikuchi-Maki, et al. Inhibitory NK Receptor Ly49Q Is Expressed on Subsets of Dendritic Cells in a Cellular Maturation- and Cytokine Stimulation-Dependent Manner. Journal of Immunology 2005. 25. Yoshiki Omatsu, Tomonori Iyoda, Yukino Kimura, Akiko Maki, Masaki Ishimori, Noriko Toyama-Sorimachi, et al. Development of Murine Plasmacytoid Dendritic Cells Defined by Increased Expression of an Inhibitory NK Receptor, Ly49Q. Journal of Immunology 2005. 26. Yumiko Kamogawa-Schifter, Jun Ohkawa, Sahori Namiki, Naoko Arai, Ken-ichi Arai, Liu Y. Ly49Q defines 2 pDC subsets in mice. Blood 2005. 27. Cao W, Bover L, Cho M, Wen X, Hanabuchi S, Bao M, et al. Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction. Journal of Experimental Medicine 2009,206:1603-1614. 28. Cao W, Bover L. Signaling and ligand interaction of ILT7: receptor-mediated regulatory mechanisms for plasmacytoid dendritic cells. Immunol Rev 2010,234:163-176. 29. Kamath A, Pooley J, Meredith AOK, David V, Yifan Z, Andrew ML, et al. The development, maturation and turnover rate of mouse spleen dendritic cell population. Journal of Immunology 2000. 30. Wilson A, Laurenti E, Oser G, van der Wath RC, Blanco-Bose W, Jaworski M, et al. Hematopoietic Stem Cells Reversibly Switch from Dormancy to Self-Renewal during Homeostasis and Repair. Cell 2008,135:1118-1129. 31. Akashi K, Traver D, Miyamoto T, Weissman IL. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 2000. 32. Kondo M, Wagers AJ, Manz MG, Prohaska SS, Scherer DC, Beilhack GF, et al. Biology of hematopoietic stem cells and progenitors: Implications for Clinical Application. Annual Review of Immunology 2003,21:759-806. 33. Rieger MA, Hoppe PS, Smejkal BM, Eitelhuber AC, Schroeder T. Hematopoietic Cytokines Can Instruct Lineage Choice. Science 2009,325:217-218. 34. Schmid MA, Kingston D, Boddupalli S, Manz MG. Instructive cytokine signals in dendritic cell lineage commitment. Immunol Rev 2010,234:32-44. 35. D'Amico A, Wu L. The early progenitors of mouse dendritic cells and plasmacytoid predendritic cells are within the bone marrow hemopoietic precursors expressing Flt3. J Exp Med 2003,198:293-303. 36. Onai N, Obata-Onai A, Schmid MA, Ohteki T, Jarrossay D, Manz MG. Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nat Immunol 2007,8:1207-1216. 37. Manz MG, Traver D, Miyamoto T, Weissman IL, Akashi K. Dendritic cell potentials of early lymphoid and myeloid progenitors. Blood 2001,97:3333-3341. 38. Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med 1992. 39. Vremec D, Lieschke GJ, Dunn AR, Robb L, Metcalf D, K. S. The influence of granulocyte/macrophage colony-stimulating factor on dendritic cell levels in mouse lymphoid organs. eur J Immunol 1997. 40. Serbina NV, Salazar-Mather TP, Biron CA, Kuziel WA, Pamer EG. TNF/iNOS-Producing Dendritic Cells Mediate Innate Immune Defense against Bacterial Infection. Immunity 2003,19:59-70. 41. Kingston D, Schmid MA, Onai N, Obata-Onai A, Baumjohann D, Manz MG. The concerted action of GM-CSF and Flt3-ligand on in vivo dendritic cell homeostasis. Blood 2009,114:835-843. 42. King IL, Kroenke MA, Segal BM. GM-CSF-dependent, CD103+ dermal dendritic cells play a critical role in Th effector cell differentiation after subcutaneous immunization. Journal of Experimental Medicine 2010,207:953-961. 43. Brasel K, De Smedt T, Smith JL, Maliszewski CR. Generation of murine dendritic cells from flt3-ligand-supplemented bone marrow cultures. Blood 2000. 44. Brasel K, McKenna H, Morrissey P, Charrier K, Morris A, Lee C, et al. Hematologic effects of flt3 ligand in vivo in mice. Blood 1996. 45. McClanahan T, Culpepper J, Campbell D, Wagner J, Franz-Bacon K, Mattson J, et al. Biochemical andgenetic characterization of multiple splice variants of the Flt3 ligand. Blood. 46. Lyman SD, SE. J. c-kit ligand and Flt3 ligand:stem/progenitor cell factors with overlapping yet distinct activities. Blood 1998. 47. Ewa Sitnicka, David Bryder, Kim Theilgaard-Mo¨ nch, Natalija Buza-Vidas, Jo¨ rgen Adolfsson, Jacobsen SEW. Key Role of flt3 Ligand in Regulation of the Common Lymphoid Progenitor but Not in Maintenance of the Hematopoietic Stem Cell Pool. Immunity 2002. 48. Kenins L, Gill JW, Boyd RL, Hollander GA, Wodnar-Filipowicz A. Intrathymic expression of Flt3 ligand enhances thymic recovery after irradiation. Journal of Experimental Medicine 2008,205:523-531. 49. Chklovskaia E. Reconstitution of dendritic and natural killer-cell subsets after allogeneic stem cell transplantation: effects of endogenous flt3 ligand. Blood 2004,103:3860-3868. 50. Marie Prat, Christelle Demarquay, Johanna Frick, Dominique Thierry, Norbert-Claude Gorin, Bertho JM. Radiation-Induced Increase in Plasma Flt3 Ligand Concentration in Mice: Evidence for the Implication of Several Cell Types. Radiation Research 2005. 51. Hilary J. McKenna, Kim L. Stocking, Robert E. Miller, Kenneth Brasel, Thibaut De Smedt, Eugene Maraskovsky, et al. Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Immunobiology 2000. 52. Waskow C, Liu K, Darrasse-Jeze G, Guermonprez P, Ginhoux F, Merad M, et al. The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nat Immunol 2008,9:676-683. 53. O'Keeffe M, Hochrein H, Vremec D, Pooley J, Evans R, Woulfe S, et al. Effects of administration of progenipoietin 1, Flt-3 ligand, granulocyte colony-stimulating factor, and pegylated granulocyte-macrophage colony-stimulating factor on dendritic cell subsets in mice. Blood 2002,99:2122-2130. 54. Karsunky H, Merad M, Cozzio A, Weissman IL, Manz MG. Flt3 ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid-committed progenitors to Flt3+ dendritic cells in vivo. J Exp Med 2003,198:305-313. 55. Maraskovsky E, Brasel K, Teepe M, Roux ER, Lyman SD, Shortman K, et al. Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. J Exp Med 1996,184:1953-1962. 56. Onai N, Obata-Onai A, Tussiwand R, Lanzavecchia A, Manz MG. Activation of the Flt3 signal transduction cascade rescues and enhances type I interferon-producing and dendritic cell development. J Exp Med 2006,203:227-238. 57. Fancke B, Suter M, Hochrein H, O'Keeffe M. M-CSF: a novel plasmacytoid and conventional dendritic cell poietin. Blood 2008,111:150-159. 58. Margit D. Witmer-Pack, Derralynn A. Hughes, Gerold Schuler, Linda Lawson, Andrew McWilliam, Kayo Inaba, et al. Identification of macrophages and dendritic cells in the osteopetrotic op/op mice. Journal of cell science 1993:1021-1029. 59. Kelli P. A. MacDonald, Vanessa Rowe, Helen M. Bofinger, Ranjeny Thomas, Tedjo Sasmono, David A. Hume, et al. The Colony-Stimulating Factor 1 Receptor Is Expressed on Dendritic Cells during Differentiation and Regulates Their Expansion. Journal of Immunology 2005. 60. Sato T, Onai N, Yoshihara H, Arai F, Suda T, Ohteki T. Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon-dependent exhaustion. Nat Med 2009,15:696-700. 61. Essers MA, Offner S, Blanco-Bose WE, Waibler Z, Kalinke U, Duchosal MA, et al. IFNalpha activates dormant haematopoietic stem cells in vivo. Nature 2009,458:904-908. 62. Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol 2005,5:375-386. 63. Chen L-S, Wei P-C, Liu T, Kao C-H, Pai L-M, Lee C-K. STAT2 hypomorphic mutant mice display impaired dendritic cell development and antiviral response. Journal of Biomedical Science 2009,16:22. 64. Naik SH, Sathe P, Park HY, Metcalf D, Proietto AI, Dakic A, et al. Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat Immunol 2007,8:1217-1226. 65. Sathaliyawala T, O'Gorman WE, Greter M, Bogunovic M, Konjufca V, Hou ZE, et al. Mammalian target of rapamycin controls dendritic cell development downstream of Flt3 ligand signaling. Immunity 2010,33:597-606. 66. Carotta S, Dakic A, D'Amico A, Pang SH, Greig KT, Nutt SL, et al. The transcription factor PU.1 controls dendritic cell development and Flt3 cytokine receptor expression in a dose-dependent manner. Immunity 2010,32:628-641. 67. Asselin-Paturel C. Type I interferon dependence of plasmacytoid dendritic cell activation and migration. Journal of Experimental Medicine 2005,201:1157-1167. 68. Cai D, Cao J, Li Z, Zheng X, Yao Y, Li W, et al. Up-regulation of bone marrow stromal protein 2 (BST2) in breast cancer with bone metastasis. BMC Cancer 2009,9:102. 69. Yoo H, Park SH, Ye SK, Kim M. IFN-gamma-induced BST2 mediates monocyte adhesion to human endothelial cells. Cell Immunol 2011,267:23-29. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41009 | - |
| dc.description.abstract | 樹突細胞(Dendritic cell, DC)是特化的免疫細胞，分布於各種淋巴器官內，以及與外界接觸的體表內側。樹突細胞可細分成conventional DC (cDC) 和plasmacytoid DC (pDC)兩種不同的亞群(subsets)，並需要持續由其前驅細胞(progenitors)分化補充；在造血系統中，巨噬細胞與樹突細胞同源前驅細胞(macrophage DC progenitors; MDP)、樹突細胞前驅細胞(common dendritic cell progenitor; CDP)以及類淋巴前驅細胞(common lymphoid progenitor; CLP)均具有分化成樹突細胞的能力，但至今，對於調節前驅細胞發育成樹突細胞的過程仍尚未全盤了解，而近年來第一型干擾素(Type I IFNs)經證實能促進造血幹細胞(hematopoietic stem cells; HSC)的分裂而產生下游血液細胞，故在本論文中，我們將探討第一型干擾素影響樹突細胞發育的相關機制。
我們使用第一型干擾素(Type I IFNs)訊息傳遞具缺陷的STAT2 (Signal transducer and activator of transcription 2) 基因突變小鼠(STAT2m/m)進行實驗，我們發現此STAT2m/m小鼠體內淋巴器官中的樹突細胞前驅細胞以及樹突細胞數目均減少。利用體外培養的方式(In Vitro)，我們發現STAT2m/m的樹突前驅細胞CDP和CLP生成樹突細胞的潛能(potential)和頻率(frequency)均有缺陷；由CDP生成的cDC較少，而CLP無法有效生成pDC。並利用過繼轉移(Adoptive transfer)實驗則證實STAT2缺乏所造成的前驅細胞缺陷是細胞自發性的(cell autonomous)。另外，其發育過程中STAT2m/m 細胞增殖(proliferation)的速度較慢，以及細胞凋亡(apoptosis)的比例也較高。同時我們也發現在STAT2m/m前驅細胞上的Fms-like tyrosine kinase-3 (Flt3)表現量較低，若使用高量的Flt3L處理STAT2m/m CLP則可挽救pDC族群的產生，顯示降低的Flt3訊息強度是造成pDC減少的原因。使用正常基因型小鼠進行的實驗結果也顯示，Flt3L可導致CLP內第一型干擾素的基因表現。同時若在體外培養或在小鼠體內使用第一型干擾素處理後的CLP會表現較高量的Flt3於其表面，並可促進樹突細胞的生成。若抑制第一型干擾素的訊息傳遞則會降低前驅細胞上Flt3的表現，並減慢細胞增殖及增加細胞凋亡，也使CLP生成pDC的能力下降。整體而言，實驗結果證實，第一型干擾素和STAT2對樹突細胞的發育扮演正面調節者(positive regulator)的角色。 | zh_TW |
| dc.description.abstract | Dendritic cells (DCs) are specialized immune cells distributed throughout the lymphoid organs and beneath the environmental contact sites. DCs are classified into conventional dendritic cell (cDC) and plasmacytoid dendritic cell (pDC) and need to be continuously replenished by hematopoietic progenitors. To date, there are, at least, three progenitors, including CDP, MDP, and CLP, with a potential to differentiate into cDC and pDC. However, the mechanisms involved in the regulation of their development and homeostasis are still not fully understood. Type I IFNs are known to promote the proliferation of hematopoietic stem cells, the origin of all blood lineages. Therefore, we would like to investigate the effects of type I IFNs on DC progenitors and DCs. Using a STAT2m/m mouse that displayed hyporesponsiveness to type I IFNs, we found that the numbers of all three DC progenitors and DC subsets were decreased. In vitro Flt3L-dependent DC development were significantly impaired in STAT2m/m mice with defective DC-forming potentials and frequencies. CDPs from STAT2m/m mice displayed a reduced potential to develop into DCs and STAT2m/m CLPs preferentially favoured the development of cDC over pDC, which was opposite to the fate of WT CLPs. Adoptive transfer of CLPs into CD45.1 congenic mice suggested that the defects in STAT2m/m CLPs were cell-intrinsic. We also observed the reduced proliferative rate and increase apoptosis rate of STAT2m/m progenitors. Moreover, Flt3 expression level was lower on all three DC progenitors of STAT2m/m mice. High dosage of Flt3L could reverse the fate determination of cDC and pDC from STAT2m/m CLP, suggesting that reduced signalling strength in the progenitors might account for the DC developmental defects. Interestingly, Flt3 signalling induced the expression of type I IFNs in CLPs. In vitro or in vivo administration of IFNα promoted the induction of Flt3 expression on progenitors and enhanced generation of both DC subsets. Blocking type I IFNs signalling attenuated Flt3L-dependent expression of Flt3, increased apoptosis, decreased proliferation and altered the DC subsets differentiation by favouring cDC generation. Taken together, these results indicated a positive role of STAT2 and type I IFNs in promoting DC precursor development and DC subsets differentiation. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-14T17:11:37Z (GMT). No. of bitstreams: 1 ntu-100-R98449004-1.pdf: 6117960 bytes, checksum: 835478b46131518a42c7289066ad7196 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 口試委員會審定書…………………………………………………………………...… i
誌謝…………………………………………………………………………………….. ii Acknowledgement……………………………………………………..………….….. iii 中文摘要………………………………………………………………………………. iv Abstract…………………………..…………………………………………………… v Abbreviations………………………………………………………………...………. vii Table of contents……………………………………………………………………… ix List of figures……………………………………………………………………… xiii Chapter I Introduction……………………………………………………………… 1 1.1 DC subsets…………………………………………………………………….. 2 1.2 DC progenitors………………………………………………………………… 5 1.3 Cytokines in DC development………………………………………………… 7 1.4 Type I IFNs in HSC homeostasis……………………………………………… 9 Chapter II Material and Methods……………………………………………….... 11 2.1 Mice……………………………………………………………………….... 12 2.2 Ex vivo analysis of DC subsets…………………………………………….. 12 2.3 Ex vivo progenitor analysis and cell sorting ………….…………………… 13 2.4 5-FU-dependent Self-reconstitution………………………………………... 14 2.5 In vitro DC cultures……………………………………………………….. 14 2.6 Flt3L preparation…………………………………………………………… 15 2.7 Stromal cell co-culture…………………………………………………….. 16 2.8 Limiting-dilution assay……………………………………………………. 17 2.9 Adoptive transfer………………………………………………………….. 17 2.10 Proliferation and apoptosis assay………………………………………… 18 2.11 Intracellular phospho-Akt staining…………………………………………. 18 2.12 In vivo hydrodynamic gene delivery……………………………………… 19 2.13 Luciferase assay for IFNa detection………………………………………... 19 2.14 Ectopic expression of Flt3 on WT MEF……………………………………. 21 2.15 RT-PCR analysis…………………………………………………………… 21 Chapter III Results………………………………………………………………… 24 3.1 Analysis of ex vivo DC subsets population………………………………... 25 3.2 Reduced in vitro Flt3L-dependent DC development in STAT2m/m BM….. 26 3.3 Reduced DC progenitors in STAT2 m/m mice……………………………… 28 3.4 Reduced in vivo reconstitution rate of DC progenitors and pDC in STAT2m/m mice…………………………..…………………………………………….. 29 3.5 DC progenitors of STAT2m/m mice displayed reduced potential to develop into DC..……………………………………………………………………. 30 3.6 Impaired pDC development from STAT2m/m CLP is cell autonomous...... 32 3.7 STAT2m/m DC progenitors display reduced proliferative rate……………... 33 3.8 STAT2m/m DC progenitors display higher apoptotic rate………………….. 34 3.9 STAT2m/m DC progenitors express lower level of Flt3 receptor…………... 35 3.10 IFNa promotes the expression of Flt3 on CLPs and DC development… 37 3.11 Flt3L induces the expression of type I IFNs………………………………... 39 3.12 Type I IFNs in combination with Flt3L regulate DC development………... 40 3.13 Blocking of type I IFN signalling increases apoptosis, decreases proliferation and Flt3 expression in response to Flt3L…………………….……. 41 Chapter IV Discussion……………………………………………………………... 43 4.1 Not all organs of STAT2m/m mice displayed reduced DC subsets phenotype..................................................................................... 45 4.2 More apparent pDC defects in STAT2m/m mice after 5-FU treatment…… 46 4.3 Different intensities of the Flt3 signal affect the DC fate determination….. 46 References……………………………………………………………………… 49 Figures………………………………………………………………………………... 61 | |
| dc.language.iso | en | |
| dc.subject | 第一型干擾素 | zh_TW |
| dc.subject | 樹突細胞前驅細胞 | zh_TW |
| dc.subject | 樹突細胞 | zh_TW |
| dc.subject | Type I IFNs | en |
| dc.subject | Flt3 signalling | en |
| dc.subject | Hematopoietic progenitors | en |
| dc.subject | STAT2 | en |
| dc.subject | Dendritic cells | en |
| dc.title | STAT2與第一型干擾素在樹突細胞發育過程中所扮演角色之研究 | zh_TW |
| dc.title | Effects of STAT2 and Type I Interferon Signals on Dendritic Cell Development | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林國儀(Kuo-I Lin),嚴仲楊(Jeffrey J. Y. Yen) | |
| dc.subject.keyword | 樹突細胞,第一型干擾素,樹突細胞前驅細胞, | zh_TW |
| dc.subject.keyword | Dendritic cells,Type I IFNs,STAT2,Hematopoietic progenitors,Flt3 signalling, | en |
| dc.relation.page | 104 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-08-12 | |
| 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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