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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李建國(Chien-Kuo Lee) | |
| dc.contributor.author | Ya-Ru Yu | en |
| dc.contributor.author | 游雅如 | zh_TW |
| dc.date.accessioned | 2022-11-23T09:10:35Z | - |
| dc.date.available | 2023-10-31 | |
| dc.date.available | 2022-11-23T09:10:35Z | - |
| dc.date.copyright | 2021-09-16 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-18 | |
| dc.identifier.citation | Akkaya, M., Kwak, K., and Pierce, S.K. (2020). B cell memory: building two walls of protection against pathogens. Nat Rev Immunol 20, 229-238. Anderson, D.A., Dutertre, C.A., Ginhoux, F., and Murphy, K.M. Genetic models of human and mouse dendritic cell development and function. Nat Rev Immunol, 15. Anderson, D.A., Dutertre, C.A., Ginhoux, F., and Murphy, K.M. (2020). Genetic models of human and mouse dendritic cell development and function. Nat Rev Immunol. Balazs, M., Martin, F., Zhou, T., and Kearney, J.F. (2002). Blood dendritic cells interact with splenic marginal zone B cells to initiate T-Independent immune responses. Immunity 17, 341-352. Bao, M.S., and Liu, Y.J. (2013). Regulation of TLR7/9 signaling in plasmacytoid dendritic cells. Protein Cell 4, 40-52. Bekeredjian-Ding, I., and Jego, G. (2009). Toll-like receptors - sentries in the B-cell response. Immunology 128, 311-323. Bekeredjian-Ding, I.B., Wagner, M., Hornung, V., Giese, T., Schnurr, M., Endres, S., and Hartmann, G. (2005). Plasmacytoid dendritic cells control TLR7 sensitivity of naive B cells via type IFN. J Immunol 174, 4043-4050. Berggren, O., Hagberg, N., Weber, G., Alm, G.V., Ronnblom, L., and Eloranta, M.L. (2012). B lymphocytes enhance interferon-a production by plasmacytoid dendritic cells. Arthritis and Rheumatism 64, 3409-3419. Carrasco, Y.R., Fleire, S.J., Cameron, T., Dustin, M.L., and Batista, F.D. (2004). LFA-1/ICAM-1 interaction lowers the threshold of B cell activation by facilitating B cell adhesion and synapse formation. Immunity 20, 589-599. Cerutti, A., Cols, M., and Puga, I. (2013). Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes. Nat Rev Immunol 13, 118-132. Colino, J., Shen, Y., and Snapper, C.M. (2002). Dendritic cells pulsed with intact Streptococcus pneumoniae elicit both protein- and polysaccharide-specific immunoglobulin isotype responses in vivo through distinct mechanisms. Journal of Experimental Medicine 195, 1-13. Corinti, S., Albanesi, C., la Sala, A., Pastore, S., and Girolomoni, G. (2001). Regulatory activity of autocrine IL-10 on dendritic cell functions. J Immunol 166, 4312-4318. Craxton, A., Magaletti, D., Ryan, E.J., and Clark, E.A. (2003). Macrophage- and dendritic cell-dependent regulation of human B-cell proliferation requires the TNF family ligand BAFF. Blood 101, 4464-4471. de Padilla, C.M.L., and Niewold, T.B. (2016). The type I interferons: Basic-concepts and clinical relevance in immune-mediated inflammatory diseases. Gene 576, 14-21. Ding, C.L., Cai, Y.H., Marroquin, J., Ildstad, S.T., and Yan, J. (2009). Plasmacytoid Dendritic Cells Regulate Autoreactive B Cell Activation via Soluble Factors and in a Cell-to-Cell Contact Manner. J Immunol 183, 7140-7149. Dubois, B., Massacrier, C., Vanbervliet, B., Fayette, J., Briere, F., Banchereau, J., and Caux, C. (1998). Critical role of IL-12 in dendritic cell-induced differentiation of naive B lymphocytes. J Immunol 161, 2223-2231. Green, N.M., Laws, A., Kiefer, K., Busconi, L., Kim, Y.M., Brinkmann, M.M., Trail, E.H., Yasuda, K., Christensen, S.R., Shlomchik, M.J., et al. (2009). Murine B Cell Response to TLR7 Ligands Depends on an IFN-beta Feedback Loop. J Immunol 183, 1569-1576. Grohmann, U., Bianchi, R., Belladonna, M.L., Vacca, C., Silla, S., Ayroldi, E., Fioretti, M.C., and Puccetti, P. (1999). IL-12 acts selectively on CD8 alpha(-) dendritic cells to enhance presentation of a tumor peptide in vivo. J Immunol 163, 3100-3105. Hartmann, G., Battiany, J., Poeck, H., Wagner, M., Kerkmann, M., Lubenow, N., Rothenfusser, S., and Endres, S. (2003). Rational design of new CpG oligonucleotides that combine B cell activation with high IFN-alpha induction in plasmacytoid dendritic cells. European Journal of Immunology 33, 1633-1641. Honda, K., Ohba, Y., Yanai, H., Negishi, H., Mizutani, T., Takaoka, A., Taya, C., and Taniguchi, T. (2005). Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction. Nature 434, 1035-1040. Huang, N.N., Han, S.B., Hwang, I.Y., and Kehrl, J.H. (2005). B cells productively engage soluble antigen-pulsed dendritic cells: visualization of live-cell dynamics of B cell-dendritic cell interactions. J Immunol 175, 7125-7134. Iwasaki, A., and Medzhitov, R. (2010). Regulation of Adaptive Immunity by the Innate Immune System. Science 327, 291-295. Janeway, C.A., and Medzhitov, R. (2002). Innate immune recognition. Annual Review of Immunology 20, 197-216. Jego, G., Palucka, A.K., Blanck, J.P., Chalouni, C., Pascual, V., and Banchereau, J. (2003). Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity 19, 225-234. Kawai, T., and Akira, S. (2007). TLR signaling. Seminars in Immunology 19, 24-32. Kishimoto, T. (2010). IL-6: from its discovery to clinical applications. Int Immunol 22, 347-352. Krystufkova, O., Helmers, S.B., Venalis, P., Malmstrom, V., Lindroos, E., Vencovsky, J., and Lundberg, I.E. (2014). Expression of BAFF receptors in muscle tissue of myositis patients with anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies. Arthritis Res Ther 16, 13. Lewis, S.M., Williams, A., and Eisenbarth, S.C. (2019). Structure and function of the immune system in the spleen. Science Immunology 4. Liu, D., Yin, X.Y., Olyha, S.J., Nascimento, M.S.L., Chen, P., White, T., Gowthaman, U., Zhang, T.T., Gertie, J.A., Zhang, B.Y., et al. (2019). IL-10-Dependent Crosstalk between Murine Marginal Zone B Cells, Macrophages, and CD8 alpha(+) Dendritic Cells Promotes Listeria monocytogenes Infection. Immunity 51, 64-+. Malefyt, R.D., Abrams, J., Bennett, B., Figdor, C.G., and Devries, J.E. (1991). Interleukin-10(IL-10) Inhibits Cytokine Sythesis by Human Monocytes - an Autoregulatory Role of IL-10 Produced by Monocytes. Journal of Experimental Medicine 174, 1209-1220. Manh, T.P.V., Bertho, N., Hosmalin, A., Schwartz-Comil, I., and Dalod, M. (2015). Investigating evolutionary conservation of dendritic cell subset identity and functions. Frontiers in Immunology 6. Merad, M., Sathe, P., Helft, J., Miller, J., and Mortha, A. (2013). The Dendritic Cell Lineage: Ontogeny and Function of Dendritic Cells and Their Subsets in the Steady State and the Inflamed Setting. In Annual Review of Immunology, Vol 31, D.R. Littman, and W.M. Yokoyama, eds. (Palo Alto: Annual Reviews), pp. 563-604. Nguyen, K.B., Watford, W.T., Salomon, R., Hofmann, S.R., Pien, G.C., Morinobu, A., Gadina, M., O'Shea, J.J., and Biron, C.A. (2002). Critical role for STAT4 activation by type 1 interferons in the interferon-gamma response to viral infection. Science 297, 2063-2066. Nutt, S.L., Hodgkin, P.D., Tarlinton, D.M., and Corcoran, L.M. (2015). The generation of antibody-secreting plasma cells. Nat Rev Immunol 15, 160-171. Obukhanych, T.V., and Nussenzweig, M.C. (2006). T-independent type II immune responses generate memory B cells. Journal of Experimental Medicine 203, 305-310. Palm, A.K.E., Friedrich, H.C., and Kleinau, S. (2016). Nodal marginal zone B cells in mice: a novel subset with dormant self-reactivity. Scientific Reports 6. Patke, C.L., and Shearer, W.T. (2000). gp120- and TNF-alpha-induced modulation of human B cell function: Proliferation, cyclic AMP generation, Ig production, and B-cell receptor expression. Journal of Allergy and Clinical Immunology 105, 975-982. Poeck, H., Wagner, M., Battiany, J., Rothenfusser, S., Wellisch, D., Hornung, V., Jahrsdorfer, B., Giese, T., Endres, S., and Hartmann, G. (2004). Plasmacytoid dendritic cells, antigen, and CpG-C license human B cells for plasma cell differentiation and immunoglobulin production in the absence of T-cell help. Blood 103, 3058-3064. Shaw, J., Wang, Y.H., Ito, T., Arima, K., and Liu, Y.J. (2010). Plasmacytoid dendritic cells regulate B-cell growth and differentiation via CD70. Blood 115, 3051-3057. Shin, E.C., Seifert, U., Kato, T., Rice, C.M., Feinstone, S.M., Kloetzel, P.M., and Rehermann, B. (2006). Virus-induced type IIFN stimulates generation of immunoproteasomes at the site of infection. Journal of Clinical Investigation 116, 3006-3014. Sichien, D., Lambrecht, B.N., Guilliams, M., and Scott, C.L. (2017). Development of conventional dendritic cells: from common bone marrow progenitors to multiple subsets in peripheral tissues. Mucosal Immunol 10, 831-844. Siegal, F.P., Kadowaki, N., Shodell, M., Fitzgerald-Bocarsly, P.A., Shah, K., Ho, S., Antonenko, S., and Liu, Y.J. (1999). The nature of the principal type 1 interferon-producing cells in human blood. Science 284, 1835-1837. Siegemund, S., Hartl, A., von Buttlar, H., Dautel, F., Raue, R., Freudenberg, M.A., Fejer, G., Buttner, M., Kohler, G., Kirschning, C.J., et al. (2009). Conventional Bone Marrow-Derived Dendritic Cells Contribute to Toll-Like Receptor-Independent Production of Alpha/Beta Interferon in Response to Inactivated Parapoxvirus Ovis. J Virol 83, 9411-9422. Tanabe, Y., Nishibori, T., Su, L., Arduini, R.M., Baker, D.P., and David, M. (2005). Cutting edge: role of STAT1, STAT3, and STAT5 in IFN-alpha beta responses in T lymphocytes. J Immunol 174, 609-613. Tang, F., Du, Q.M., and Liu, Y.J. (2010). Plasmacytoid dendritic cells in antiviral immunity and autoimmunity. Science China-Life Sciences 53, 172-182. Tessarz, A.S., Weiler, S., Zanzinger, K., Angelisova, P., Horejsi, V., and Cerwenka, A. (2007). Non-T cell activation linker (NTAL) negatively regulates TREM-1/DAP12-Induced inflammatory cytokine production in myeloid cells. J Immunol 178, 1991-1999. Tezuka, H., Abe, Y., Asano, J., Sato, T., Liu, J.J., Iwata, M., and Ohteki, T. (2011). Prominent Role for Plasmacytoid Dendritic Cells in Mucosal T Cell-Independent IgA Induction. Immunity 34, 247-257. Thibault, D.L., Graham, K.L., Lee, L.Y., Balboni, I., Hertzog, P.J., and Utz, P.J. (2009). Type I interferon receptor controls B-cell expression of nucleic acid-sensing Toll-like receptors and autoantibody production in a murine model of lupus. Arthritis Res Ther 11, 10. Vincent, F.B., Saulep-Easton, D., Figgett, W.A., Fairfax, K.A., and Mackay, F. (2013). The BAFF/APRIL system: Emerging functions beyond B cell biology and autoimmunity. Cytokine Growth Factor Reviews 24, 203-215. Watts, C., West, M.A., and Zaru, R. (2010). TLR signalling regulated antigen presentation in dendritic cells. Curr Opin Immunol 22, 124-130. Whittaker, G.C., Orr, S.J., Quigley, L., Hughes, L., Francischetti, I.M.B., Zhang, W.G., and McVicar, D.W. (2010). The Linker for Activation of B Cells (LAB)/Non-T Cell Activation Linker (NTAL) Regulates Triggering Receptor Expressed on Myeloid Cells (TREM)-2 Signaling and Macrophage Inflammatory Responses Independently of the Linker for Activation of T Cells. Journal of Biological Chemistry 285. Xu, W., Joo, H., Clayton, S., Dullaers, M., Herve, M.C., Blankenship, D., De La Morena, M.T., Balderas, R., Picard, C., Casanova, J.L., et al. (2012). Macrophages induce differentiation of plasma cells through CXCL10/IP-10. Journal of Experimental Medicine 209, 1813-1823. Yousif, A.S., Ronsard, L., Shah, P., Omatsu, T., Sangesland, M., Moreno, T.B., Lam, E.C., Vrbanac, V.D., Balazs, A.B., Reinecker, H.C., et al. (2021). The persistence of interleukin-6 is regulated by a blood buffer system derived from dendritic cells. Immunity 54, 235. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79770 | - |
| dc.description.abstract | "B細胞可以藉由胸腺依賴性或非依賴性的途徑活化。在缺乏胸腺細胞（主要是T細胞）幫助的情況下，B細胞會接收其他細胞提供的訊號促進胸腺非依賴性反應。過去研究已知漿狀樹突細胞(plasmacytoid dendritic cell, pDC)在經由類鐸受體 (Toll-like receptor, TLR) 刺激時可以產生大量的第一型干擾素(type I interferon, IFN-I)，並且藉由IFN-I促進B細胞的胸腺非依賴性反應。然而傳統樹突細胞 (conventional dendritic cell, cDC) 在其中所扮演的角色仍不明確。我們的研究發現cDC可以藉由胸腺非依賴性的方式促進B細胞反應。當B細胞和骨髓所分化的傳統樹突細胞 (bone marrow-derived cDC, BM-cDC) 共同培養並且以CpG (TLR9配體) 刺激時，除了細胞增殖外，其活化、分化以及細胞激素產量相較B細胞單獨培養都有顯著的提升。有趣的是，cDC可以在缺乏IFN-I訊號的情況下促進B細胞活化，代表cDC可以藉由IFN-I以外的訊號幫助B細胞。然而，與B細胞相反，在兩種細胞共同培養時cDC的功能卻會受到抑制，其活化和細胞激素產量會下降。除此之外，我們發現雖然cDC1和cDC2都可以促進B細胞反應，但兩者對於FO B和MZ B細胞(兩個B細胞亞群)的調控有所不同。cDC1傾向於促進MZ B細胞活化，而cDC2則傾向促進FO B細胞活化。另外，cDC1主要藉由細胞與細胞接觸方式調控B細胞反應，而cDC2相較於cDC1會產出較多促發炎性的細胞激素，但其產量卻會受到FO B和MZ B抑制。相反的，當cDC1和MZ B共同培養時，有些細胞激素的分泌 (例如：IFN-I、IL-1、細胞趨化因子和IL-10則會上升。在體外培養系統中，當受到Streptococcus pneumoniae (S. pneumoniae) 刺激時，cDC也可以促進FO B或MZ B細胞活化。此外，在活體動物實驗中，小鼠受到S. pneumoniae刺激後脾臟中的cDC1會遷移到邊緣區 (marginal zone)，並且和MZ B細胞接觸。總而言之，我們證實在TLR9刺激下，cDC可以促進B細胞反應。另外，在受到病原體感染時，cDC1和MZ B細胞間有較強的協同作用反應，這可能在感染初期的免疫反應中扮演重要角色。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-23T09:10:35Z (GMT). No. of bitstreams: 1 U0001-1608202114082700.pdf: 6229529 bytes, checksum: 9ad569eab3acce5d0f9ac90f016b538c (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "致謝……………………………………………………………………………………………………………………………………………………………………………………………………………………i 摘要…………………………………………………………………………………………………………………………………………………………………………………………………………………ii Abstract……………………………………………………………………………………………………………………………………………………………………………………………………iii Abbreviations……………………………………………………………………………………………………………………………………………………………………………………………v Content…………………………………………………………………………………………………………………………………………………………………………………………………………vi Chapter 1 Introduction……………………………………………………………………………………………………………………………………………………2 1.1 T-independent B cell activation ……………………………………………………………………………………………………………………2 1.2 B cell subsets …………………………………………………………………………………………………………………………………………………………………3 1.3 Dendritic cell subsets ……………………………………………………………………………………………………………………………………………5 1.4 Cooperation between pDCs and B cells in TI humeral immune response ………………………7 1.5 cDCs and B cell interaction ………………………………………………………………………………………………………………………………8 1.6 Known mechanisms for DC-mediated enhancement of B cell response ………………………………8 1.7 Rationale and specific aims ………………………………………………………………………………………………………………………………9 1.8 Significance ……………………………………………………………………………………………………………………………………………………………………10 Chapter 2 Materials and Methods ………………………………………………………………………………………………………………………12 2.1 Mice …………………………………………………………………………………………………………………………………………………………………………………………12 2.2 Flow cytometry ………………………………………………………………………………………………………………………………………………………………12 2.3 Cell sorting ……………………………………………………………………………………………………………………………………………………………………13 2.4 BM-cDCs culture ……………………………………………………………………………………………………………………………………………………………13 2.5 B/cDC coculture system …………………………………………………………………………………………………………………………………………14 2.6 Proliferation assay …………………………………………………………………………………………………………………………………………………14 2.7 Enzyme-Linked Immunosorbent Assay (ELISA) ………………………………………………………………………………………15 2.8 Intracellular staining …………………………………………………………………………………………………………………………………………15 2.9 Isolation of B cells and cDCs from the coculture system …………………………………………………16 2.10 RT-QPCR …………………………………………………………………………………………………………………………………………………………………………………17 2.11 Transwell assay ……………………………………………………………………………………………………………………………………………………………17 2.12 LEGENDplex beads-based immunoassay …………………………………………………………………………………………………………18 2.13 Cryosection and immunofluorescence staining …………………………………………………………………………………18 2.14 Statistical analysis ………………………………………………………………………………………………………………………………………………19 2.15 Primary antibodies ……………………………………………………………………………………………………………………………………………………20 2.16 Secondary antibodies ………………………………………………………………………………………………………………………………………………20 Chapter 3 Results ……………………………………………………………………………………………………………………………………………………………22 3.1 cDCs enhance TLR7-mediated proliferation, activation and differentiation of B cells…………………………………………………………………………………………………………………………………………………………………………………………22 3.2 IFN-I signaling is required for cDC-dependent, TLR7-mediated enhancement of B cell activation and proliferation ……………………………………………………………………………………………………………23 3.3 BM-cDCs significantly enhance TLR9-mediated B cell activation in the absence of IFN-I signal ……………………………………………………………………………………………………………………………………………………………24 3.4 Cell-to-cell contact plays a role in cDC-mediated enhancement of activation, but not differentiation of B cells in response to CpG ………………………………………………………25 3.5 Coculture of cDCs with B cells upregulates BAFF on cDCs and increases BAFFR expression on B cells ……………………………………………………………………………………………………………………………………………26 3.6 cDCs upregulate cytokine production in cocultured-B cells in an IFN-I signal independent manner………………………………………………………………………………………………………………………………………………………27 3.7 B cells down-regulate CpG-stimulated expression and production of proinflammatory cytokines in cDCs and activation of cDCs…………………………………………………28 3.8 cDC-mediated enhancement of B cell activation is independent of CXCL10 …………30 3.9 cDC1s have higher potency to enhance the activation of MZ B cells while cDC2s preferentially enhance the activation and differentiation of FO B cells ………30 3.10 Cell-to-cell contact is important in both cDC1 and cDC2-mediated enhancement of B cell activation ………………………………………………………………………………………………………………………………………………32 3.11 IFN-I is a cytokine critical for cDC2 but not cDC1-mediated enhancement of B cell activation………………………………………………………………………………………………………………………………………………………………33 3.12 cDCs promote the activation of B cells in response to Streptococcus pneumoniae …………………………………………………………………………………………………………………………………………………………………………34 3.13 cDC1s migrate to marginal zone in response to S. pneumoniae challenge in vivo ………………………………………………………………………………………………………………………………………………………………………………………………………35 Chapter 4 Discussion ……………………………………………………………………………………………………………………………………………………38 4.1 The role of cDCs in B cell activation, proliferation and differentiation in T-independent manner…………………………………………………………………………………………………………………………………………………38 4.2 The mechanism of cDC-mediated enhancement of T-independent B cell response ………………………………………………………………………………………………………………………………………………………………………………………………………39 4.3 B cells negatively regulate cDC activation ……………………………………………………………………………………41 4.4 The differential interactions between different subsets of B cells and cDCs ………………………………………………………………………………………………………………………………………………………………………………………………………42 4.5 The interaction between MZ B cells and cDC1s ………………………………………………………………………………43 Chapter 5 Figures ……………………………………………………………………………………………………………………………………………………………45 Chapter 6 References ……………………………………………………………………………………………………………………………………………………87" | |
| dc.language.iso | en | |
| dc.subject | 肺炎鏈球菌 | zh_TW |
| dc.subject | B細胞 | zh_TW |
| dc.subject | 邊緣區B細胞 | zh_TW |
| dc.subject | 傳統樹突細胞 | zh_TW |
| dc.subject | 非胸腺依賴性反應 | zh_TW |
| dc.subject | 類鐸受體 | zh_TW |
| dc.subject | 第一型干擾素 | zh_TW |
| dc.subject | 細胞與細胞間接觸 | zh_TW |
| dc.subject | Toll-like receptor | en |
| dc.subject | cell-to-cell contact | en |
| dc.subject | Type I interferon | en |
| dc.subject | B cell | en |
| dc.subject | Marginal zone B cell | en |
| dc.subject | Conventional dendritic cell | en |
| dc.subject | T-independent response | en |
| dc.subject | Streptococcus pneumoniae | en |
| dc.title | 傳統樹突細胞亞群的差異影響胸腺非依賴性 B 細胞的反應 | zh_TW |
| dc.title | Differential Effects of Conventional Dendritic Cell Subsets on Enhancing T-independent B cell Response | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林國儀(Hsin-Tsai Liu),徐立中(Chih-Yang Tseng) | |
| dc.subject.keyword | B細胞,邊緣區B細胞,傳統樹突細胞,非胸腺依賴性反應,類鐸受體,第一型干擾素,細胞與細胞間接觸,肺炎鏈球菌, | zh_TW |
| dc.subject.keyword | B cell,Marginal zone B cell,Conventional dendritic cell,T-independent response,Toll-like receptor,Type I interferon,cell-to-cell contact,Streptococcus pneumoniae, | en |
| dc.relation.page | 91 | |
| dc.identifier.doi | 10.6342/NTU202102393 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2021-08-19 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| dc.date.embargo-lift | 2023-10-31 | - |
| 顯示於系所單位： | 免疫學研究所 | |
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| U0001-1608202114082700.pdf | 6.08 MB | Adobe PDF | 檢視/開啟 |
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