研究幼鼠和成鼠在氣喘動物模式誘發口服耐受性的差異性

Study on the Differences between Infant and Adult Mice during the Development of Oral Tolerance in A Murine Model of Allergic Asthma

廖季萍(Chi-Ping Liao)

指導教授 ： 江伯倫

國立臺灣大學/牙醫專業學院/口腔生物科學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.02316

摘要

利用口服特定的抗原可以誘導口服耐受性(oral tolerance)的發生，以降低抗原特異性免疫反應。此口服耐受性的現象可以應用於過敏性疾病的治療。過去許多研究發現，輔助T細胞(T helper cells)在幼年時期會傾向於過敏反應的第二型輔助T細胞(Th2)，而IL-12則被普遍認為是參與第一型輔助T細胞的分化有關的細胞激素。另外，有些研究認為DNA 甲基化在附基因調控(epigenetic regulation)中與影響基因的表現及細胞生長分化等功能有關。因此，此研究中，利用氣喘動物模式誘發口服耐受性的機制比較三週齡小鼠和八週齡小鼠之間的差異性。首先，在帶有OVA-T細胞受器(OVA-T cell receptor)基因的基因轉殖小鼠之六至八週齡鼠中成功建立氣喘動物模式。在連續五天口服餵食成鼠OVA 抗原(10 mg/day或100 mg/day)後，結果顯示能有效緩解呼吸道阻力、減輕肺部發炎細胞浸潤現象及降低血清中抗原特異性IgE抗體的產生。然而，相較於八週齡小鼠過敏性氣喘組別，所有的三週齡小鼠皆顯著地降低過敏氣喘現象。此外，三週齡小鼠的脾臟細胞在體外刺激培養後，第二型輔助T細胞細胞激素IL-4的分泌顯著減少，而有些研究推斷幼年時期可能會產生保護性的反應而偏向第一型輔助T細胞(Th1)。然而在IL-12基因甲基化的研究中發現三週齡小鼠與八週齡小鼠於IL-12基因啟動子(promoter)位置皆有甲基化的產生，因此推論IL-12基因啟動子的甲基化可能並非造成小鼠在幼年時期降低過敏反應的主要機制。由本實驗結果推論三週齡的小鼠無法誘發過敏反應可能與免疫系統在不同年齡的成熟度有關，因而造成不同發展的傾向，而更多的推論仍需待更進一步的研究證實。

關鍵字

三週齡小鼠 ； 氣喘 ； DNA甲基化 ； 介質12 ； 口服耐受性

並列摘要

Oral tolerance has been defined as the lack of systemic immune response that formerly exposed to the same antigen and this characteristic phenomenon might be used as a potential therapeutic approach for allergic diseases, such as asthma. Several studies indicate that T helper cells in early life induce a strong bias towards Th2 function which plays a role in allergic immune response. DNA methylaion is an important epigenetic regulation involved in regulating gene expression and development of cell lineages. Therefore, in this study we would like to compare the different effects on orally delivered antigen to the murine model of asthma between 3-week-old and 8-week-old mice. In this study, we established the animal model of asthma in adult OVA-TCR transgenic mice. Then oral tolerance was induced by feeding 10 mg/day and 100 mg/day of OVA in 8-week-old mice could suppress the response of asthma, such as airway hyperresponsiveness, antigen specific IgE production and eosinophilia, by contrast, were obviously lower than in all 3-week-old mice groups compared to asthmatic group of 8-week-old mice. The levels of IL-4 produced by splenocyte waslower significantly in all 3-week-old groups which probably prone to the protective Th1 response in early life. Whereas methylation of IL-12 gene promoter occurs in either 3-week-old or 8-week-old mice suggested that is not a main mechanism to decrease the
inflammatory response in early life of infant mice. In this study, we demonstrated that 3-week-old mice had less immune response with OVA sensitization. More are needed to clarify the phenomenon, however, mutation of immune system might be different with ages.

並列關鍵字

3-week-old mice ； asthma ； DNA methylation ； IL-12 ； oral tolerance

參考文獻

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