- 學位論文
樹突細胞在肺部發炎的雙重角色探討: 耐受性及促敏性
Study on the dual roles of dendritic cells in pulmonary inflammation: tolerogenicity and immunogenicity
摘要
前言：樹突細胞（DCs）在免疫系統中扮演了左右後天免疫反應的關鍵角色，本研究探討了樹突細胞在主導免疫反應發展時的兩個面向：對於抗原的耐受性調節，以及過敏疾病發展過程中之促敏性。 實驗設計：利用CoPP藥物誘導小鼠骨髓樹突細胞產生HO-1蛋白，探討DCs本身免疫耐受性的特徵以及對調節性T細胞的影響。另一方面探討了DCs在促進發炎的過程中，Aryl hydrocarbon receptor（AhR）在其中的機制，以及在小鼠疾病模式中的角色。 結果：經CoPP處理後之小鼠骨髓樹突細胞，其整體的成熟度下降，同時降低了促發炎細胞激素的分泌但提高IL-10的表現，更可在體內外皆誘導出較高量的調節性T細胞，並且可在氣喘動物模式中降低發炎反應的強度。在模擬人類吸入空氣汙染分子並引發過敏性氣喘的小鼠模式中，我們除了發現南台灣空汙主要分子Indeno[1,2,3-cd]pyrene（IP）是扮演增強過敏反應的輔助因子以及其可增加氧化壓力的特性外，更得知DCs在執行致敏反應時AhR訊息傳遞路徑的重要性。 結論：由實驗結果顯示，CoPP處理後之樹突細胞會產生免疫耐受的特性，並進一步的促進抗原專一性調節性T細胞族群的分化，也發現空氣污染的曝露確實和過敏性氣喘的盛行率提高有關，這些研究將有助於發展自體免疫疾病或過敏性氣喘等抗原特異性的免疫療法。
並列摘要
BACKGROUD: Dendritic cells (DCs) play a key role in modulating immune response. This study disscuss about the two different features when DCs directing immune response: tolerogenic and allergenic. DESIGN: Murine bone marrow derived dendritic cells were treated with CoPP (HO-1 inducer). Explore the tolerogenic feature of DCs and regulatory T cell induction ability. On the other hand, the mechanism of the aryl hydrocarbon receptor (AhR) in the process of promoting inflammation of DCs and its role in the disease model were discussed. RESULTS: The CoPP-treated mouse bone marrow dendritic cells have a reduced overall maturation and the secretion of pro-inflammatory cytokines but increase IL-10, and induce a higher amount of regulatory T cells both in vitro and in vivo. CoPP treated DCs also reduce the inflammatory intensity in asthmatic animal models. In the mouse model that simulates human inhalation of air pollution molecules and triggers allergic asthma, we not only found that Indeno [1,2,3-cd]pyrene (IP), the main molecule of air pollution in southern Taiwan, acts as a cofactor for enhancing allergic response and increased oxidative stress, but also revealed the importance of the AhR signaling pathway in DCs. CONCLUSIONS: We demonstrate that CoPP-DCs have tolerogenic phenotype and further promote the differentiation of antigen-specific regulatory T cell populations. It has also been found that air pollution exposure does increase the prevalence of allergic asthma. These findings will help develop antigen-specific immunotherapy such as autoimmune diseases or allergic asthma.