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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳漪紋(Yi-Wen Chen) | |
| dc.contributor.author | Chi-Lun Lan | en |
| dc.contributor.author | 藍啟綸 | zh_TW |
| dc.date.accessioned | 2023-03-19T22:34:38Z | - |
| dc.date.copyright | 2022-10-05 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-08-23 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84953 | - |
| dc.description.abstract | 研究背景：鈦金屬是公認最廣為使用之植體材料，然而鈦金屬過敏的問題近年來也日趨受到重視。此外，相較於牙周炎，植體周圍發炎的免疫病理機轉以及其與系統性共病症之關聯仍尚未明瞭。有鑒於此，本篇研究的目的為探討鈦金屬在植體周圍微環境與頸部淋巴結所造成的T細胞介導免疫之轉變。 材料與方法：本研究於三種不同層面，探索以鈦金屬為基底之材料對於T細胞免疫的影響，分別為(1)將美國國家生物技術資訊中心(NCBI)的基因表現資料庫(GEO)中，所取得之大鼠植體周圍組織與健康連接上皮之轉錄組資料進行生物資訊分析;(2)體外實驗:於鈦板上培養人類周邊血液單核細胞，分析T細胞免疫的表型與功能性變化;以及(3)體內實驗:於小鼠上顎植入客製化鈦植體，分析其頸部淋巴結中T細胞介導免疫之轉變。 結果：於生物資訊分析與人類周邊血液單核細胞培養的結果中，顯示鈦金屬會促進alpha-beta T細胞的活化，並誘發T細胞之分化朝向發炎型的T細胞亞群，以及增進發炎性細胞激素的分泌。此外，於小鼠實驗中，除了觀察到鈦植體造成頸部淋巴結腫大外，流式細胞儀分析的結果顯示於小鼠頸部淋巴結中，Th1, Th17與Tc1亞群有顯著地較控制組活化與增加，而Treg亞群則是顯著地較控制組減少。 結論：鈦金屬植體的植入會造成植體周圍微環境與頸部淋巴結處T細胞的活化，並且會促使輔助型T細胞(Th)與細胞毒性T細胞(Tc)往發炎性表型進行分化。本研究結果也提供了植體周圍發炎與系統性共病症之間的可能關聯以及T細胞免疫調節應用於植體周圍發炎等未來研究之方向。 | zh_TW |
| dc.description.abstract | Research background: Titanium was generally acknowledged as the most commonly used fixture material in implant dentistry. Nevertheless, titanium hypersensitivity has gained increasing attention recently. In addition, unlike the well-established association between periodontitis and systemic inflammatory complications, the immunopathogenesis of peri-implant inflammation and its relationship with systemic comorbidities remain unclear. Therefore, the aim of this research is to investigate the titanium-induced alteration in T cell-mediated immunity in both peri-implant microenvironment and cervical lymph nodes. Materials and methods: In the present study, the influence of titanium-based materials on T cell immunity was explored at different levels through (1) the bioinformatic analysis of transcriptomic profiles, obtained from National Center for Biotechnology Information - Gene Expression Omnibus database, comparing peri-implant epithelium with healthy junctional epithelium of a rat model, (2) in vitro analysis of phenotypic and functional changes in T cell immunity by human peripheral blood mononuclear cells cultured on titanium discs, and (3) in vivo validation of altered T cell-mediated immunity in cervical lymph nodes by titanium implantation in a murine model. Result: The analyses of transcriptomic profiles and in vitro cell culture indicated that titanium promoted alpha-beta T cell activation and further provoked the differentiation of T cells towards inflammatory subpopulations as well as the upregulation of corresponding inflammatory cytokines. Moreover, in vivo implant-associated lymphadenitis model revealed the preferential activation of Th1, Th17, Tc1 cells, and downregulation of Tregs in cervical lymph nodes after titanium implant placement by high-dimensional flow cytometry. Conclusion: With the limitation of the study, it is concluded that activated T cell- mediated immunity is observed in both peri-implant microenvironment and cervical lymph nodes. Titanium implants drive helper and cytotoxic T cells to more inflammatory phenotypes in the initial phase. The results of the present study imply the viability of T-cell immunomodulation for the management of peri-implant inflammation and foreground the pivotal role of T cell immunity in peri-implant inflammation and possible systemic inflammatory comorbidities following titanium implant placement. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-19T22:34:38Z (GMT). No. of bitstreams: 1 U0001-2208202217050600.pdf: 3934601 bytes, checksum: f2ed4060a7068919f9b0f1d5052afe68 (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 口試委員會審定書 i 誌謝 ii 中文摘要 iv ABSTRACT v CONTENTS vii LIST OF FIGURES x LIST OF TABLES xii Chapter 1 Introduction 1 1.1 Implant dentistry 1 1.1.1 Osseointegration 1 1.1.2 Implant materials 1 1.1.2.1 Titanium implants 1 1.1.2.2 Zirconia implants 3 1.2 Peri-implant diseases 3 1.2.1 Peri-implant health 5 1.2.2 Peri-implant mucositis 5 1.2.3 Peri-implantitis 6 1.2.4 Current concepts and modalities in the treatment of peri-implantitis 8 1.3 T cell immunity 11 1.3.1 T cell development 11 1.3.2 T cell activation 12 1.3.2.1 Signal I (Activation) 12 1.3.2.2 Signal II (Survival) 12 1.3.2.3 Signal III (Differentiation) 13 1.3.3 T cell subpopulations and functions 14 Chapter 2 Research Motivation and Research Purposes 16 2.1 Research Motivation 16 2.2 Research Purposes 16 Chapter 3 Materials and Methods 17 3.1 Microarray data analyses 17 3.2 In vitro assessment of T cell activation in human PBMCs 17 3.2.1 Staining protocol 18 3.2.2 ELISA protocol 19 3.3 In vivo assessment of T cell differentiation in cervical lymph nodes (CLNs) 21 3.3.1 Staining protocol for Treg 21 3.3.2 Staining protocol for Th1/ Th17/ Tc1/ Tc17 23 3.4 Statistical analysis 28 Chapter 4 Result 29 4.1 Activation of T cells in the peri-implant epithelium of rats after titanium implant placement and in human peripheral blood cultured on titanium discs 29 4.2 Titanium-based materials promote differentiation to inflammatory Th1 and Th17 subpopulations and inhibit Treg population 36 4.3 Activation of T cells in CLNs after titanium implant placement in the maxillary edentulous region of a murine model 47 4.4 Orchestrated T cell-mediated immunity towards inflammatory phenotypes in CLNs of implanted mice 55 Chapter 5 Discussion 64 5.1 T cell-mediated immunity in titanium implants 64 5.2 Future perspectives 65 5.2.1 Mesenchymal stem cells (MSCs) and immunomodulatory therapy for peri-implant inflammation 65 5.2.2 Immunogenicity comparison for novel implant biomaterials 67 Chapter 6 Conclusion 69 Reference: 70 LIST OF FIGURES Figure. 1 Classification of periodontal and peri-implant diseases and conditions [14]. 4 Figure. 2 Decision making process for the treatment of peri-implant diseases [32]. 10 Figure. 3 Human PBMCs were cultured on titanium alloy discs (left) and on control culture plates (right) in vitro. 26 Figure. 4 The geometric parameters of the customized titanium implants. 26 Figure. 5 Customized titanium implants (CP grade IV titanium) were placed in the bilateral maxillary edentulous regions of the mice in experimental group of the in vivo study assessing the T cell differentiation in CLNs. 27 Figure. 6 Pathway analysis for the top 20 clusters of functional enrichment of the transcriptomic profiles in peri-implant epithelium (PIE), compared to the profiles in healthy junctional epithelium (JE). 31 Figure. 7 Representative data of the frequency of human CD25+ T cells assessed by flow cytometry. 32 Figure. 8 Representative data of the frequency of human CD25+ T cells assessed by flow cytometry. 33 Figure. 9 Pooled data of the frequency of human CD25+ T cells assessed by flow cytometry. 34 Figure. 10 Mechanisms involved in the activation of helper T cells, as predicted with MAP tool of IPA comparing transcriptomic profiles of PIE to JE. 38 Figure. 11 Mechanisms involved in the differentiation of helper T cells, as predicted with MAP tool of IPA comparing transcriptomic profiles of PIE to JE. 39 Figure. 12 The expression levels of IFN-γ assessed by ELISA. 41 Figure. 13 The expression levels of IL-17 assessed by ELISA. 43 Figure. 14 The expression levels of IL-10 assessed by ELISA. 45 Figure. 15 Comparison of the CLNs of a C57BL/6J mouse with titanium implants placed in the maxilla (A) and the CLNs of a control mouse without implants (B). 48 Figure. 16 Representative data of the frequency of CD4+ T cells and CD8+ T cells in the harvested CLNs assessed by flow cytometry. 49 Figure. 17 Pooled data of the frequency of CD4+ T cells and CD8+ T cells in the harvested CLNs assessed by flow cytometry. 50 Figure. 18 Representative data of the frequency of CD25+CD4+ T cells and CD25+CD8+ T cells in the harvested CLNs assessed by flow cytometry. 52 Figure. 19 Pooled data of the frequency of CD25+CD4+ T cells and CD25+CD8+ T cells in the harvested CLNs assessed by flow cytometry. 53 Figure. 20 The Uniform Manifold Approximation and Projection (UMAP) concatenating inflammatory T-cell subpopulations of Th1, Th17, Tc1, and Tc17 in CLNs. 57 Figure. 21 Representative data of the frequency of Th1/ Th17 CD4+ T subsets and Tc1/ Tc17 CD8+ T subsets in the harvested CLNs assessed by flow cytometry. 58 Figure. 22 Pooled data of the frequency of Th1/ Th17 CD4+ T subsets and Tc1/ Tc17 CD8+ T subsets in the harvested CLNs assessed by flow cytometry. 59 Figure. 23 Representative data of the frequency of CD4+ Treg subset and CD8+ Treg subset in the harvested CLNs assessed by flow cytometry. 61 Figure. 24 Pooled data of the frequency of CD4+ Treg subset and CD8+ Treg subset in the harvested CLNs assessed by flow cytometry. 62 LIST OF TABLES Table. 1 The frequency (%) of human activated T cells assessed by flow cytometry in each subgroup. Activated T cells were captured via gating CD3+/CD25+ cells. 35 Table. 2 Comparison of fold changes in different gene expression between peri-implant epithelium (PIE) and healthy junctional epithelium (JE) in the rat model. 40 Table. 3 The expression levels of IFN-γ (pg/ml) assessed by ELISA in each subgroup. 42 Table. 4 The expression levels of IL-17 (pg/ml) assessed by ELISA in each subgroup. 44 Table. 5 The expression levels of IL-10 (pg/ml) assessed by ELISA in each subgroup. 46 Table. 6 The frequency (%) of CD4+ T cells and CD8+ T cells in the harvested CLNs assessed by flow cytometry. 51 Table. 7 The frequency (%) of CD25+CD4+ T cells and CD25+CD8+ T cells in the harvested CLNs assessed by flow cytometry. 54 Table. 8 The frequency (%) of Th1 and Th17 subsets in the harvested CLNs assessed by flow cytometry. 60 Table. 9 The frequency (%) of Tc1 and Tc17 subsets in the harvested CLNs assessed by flow cytometry. 60 Table. 10 The frequency (%) of CD4+ Treg subset and CD8+ Treg subset in the harvested CLNs assessed by flow cytometry. 63 | |
| dc.language.iso | en | |
| dc.subject | 植體周圍發炎 | zh_TW |
| dc.subject | 鈦金屬 | zh_TW |
| dc.subject | 免疫調節 | zh_TW |
| dc.subject | T細胞 | zh_TW |
| dc.subject | 植體 | zh_TW |
| dc.subject | immunomodulation | en |
| dc.subject | Titanium | en |
| dc.subject | implants | en |
| dc.subject | peri-implant inflammation | en |
| dc.subject | T cells | en |
| dc.title | 鈦金屬於植體周圍微環境與頸部淋巴結誘發之T細胞介導免疫 | zh_TW |
| dc.title | Titanium-induced T cell-mediated immunity in peri-implant microenvironment and cervical lymph nodes | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 郭瑋庭(Wei-Ting Kuo),侯欣翰(Hsin-Han Hou) | |
| dc.subject.keyword | 鈦金屬,植體,植體周圍發炎,T細胞,免疫調節, | zh_TW |
| dc.subject.keyword | Titanium,implants,peri-implant inflammation,T cells,immunomodulation, | en |
| dc.relation.page | 75 | |
| dc.identifier.doi | 10.6342/NTU202202660 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2022-08-23 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 臨床牙醫學研究所 | zh_TW |
| dc.date.embargo-lift | 2022-10-05 | - |
| 顯示於系所單位： | 臨床牙醫學研究所 | |
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