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標題: | 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 Titanium-induced T cell-mediated immunity in peri-implant microenvironment and cervical lymph nodes |
作者: | Chi-Lun Lan 藍啟綸 |
指導教授: | 陳漪紋(Yi-Wen Chen) 陳漪紋(Yi-Wen Chen | yiwenchen@ntu.edu.tw | ), |
關鍵字: | 鈦金屬,植體,植體周圍發炎,T細胞,免疫調節, Titanium,implants,peri-implant inflammation,T cells,immunomodulation, |
出版年 : | 2022 |
學位: | 碩士 |
摘要: | 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。 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84953 |
DOI: | 10.6342/NTU202202660 |
全文授權: | 同意授權(限校園內公開) |
電子全文公開日期: | 2022-10-05 |
顯示於系所單位: | 臨床牙醫學研究所 |
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