伴隨著奈米科技的蓬勃發展，奈米材料的應用也越來越廣泛，其中單層奈米碳管因高彈性、良好導電性的物質特性，已被廣泛應用於電子行業、電力儲存裝置、超導產品以及航空航太等。然而，奈米材料的吸入對人體所造成的潛在傷害以及其機制尚未釐清。根據先前動物研究指出，單層奈米碳管的暴露會引起小鼠肺部損傷、肉芽腫、上皮細胞間質轉化及纖維化的情形發生。樹突細胞為已知重要的抗原呈現細胞，將捕捉到的抗原呈現給T細胞，引發免疫反應。在本研究中，假設單層奈米碳管造成肺部損傷的微環境，誘導樹突細胞活化引發T細胞免疫反應及纖維化的發生。本篇研究主要去釐清單層奈米碳管暴露後，不同樹突細胞的生成變化和其對T細胞變化及肺纖維化產生的影響。使用C57BL6母鼠以口咽吸入方式暴露單層奈米碳管，暴露劑量為80 μg/mouse，分別至不同時間點(3天、1週、2週、4週、8週、12週)後犧牲。利用流式細胞儀分析定量3種不同類型之樹突細胞，包含CD11c+lowCD11b+MHCII+CD207+的蘭格漢氏樹突細胞、CD11c+highCD11b+lowMHCII+CD103+的發炎性CD103+樹突細胞以及CD11c+highCD11b+highMHCII+CD103- 的單核細胞衍生之樹突細胞進行定量分析。利用不同細胞標誌針對各種T淋巴細胞進行分型定量，包含第二型輔助T細胞(Th2; CD4+IL-4+)、第十七型輔助T細胞(Th17; CD4+IL17-A+)以及調節性T細胞(Treg; CD4+CD25+FoxP3+)。利用酵素連結免疫分析法量測CCL2、CCL19、CCL12、 CXCL21、IL17、GM-CSF以及TGF-β。此外，利用口服灌食方式給予已知樹突細胞抑制劑(VAG539)，目的為進一步驗證樹突細胞在由單層奈米碳管所誘發之肺纖維化的貢獻。結果顯示肺部CCL2、CCL19、CCL12、 CXCL21、IL17、GM-CSF以及TGF-β在暴露單層奈米碳管第三天後濃度顯著上升。接著在流式細胞儀分析結果指出，暴露單層奈米碳管第三天後，三種不同型態的樹突細胞(包含CD11c+lowCD11b+MHCII+CD207+ 的蘭格漢氏樹突細胞、CD11c+highCD11b+lowMHCII+CD103+的發炎性CD103+樹突細胞以及CD11c+highCD11b+highMHCII+CD103- 的單核細胞衍生之樹突細胞)均顯著於肺部聚集，並分別於第二週及第四週時達到峰，第二型輔助T細胞於暴露單層奈米碳管第三天時顯著上升，第十七型輔助T細胞以及調節性T細胞於暴露一週時顯著上升，並均在暴露第四週時達到峰。在體外試驗的部分，小鼠暴露單層奈米碳管後，分離出脾臟細胞進行T細胞增生能力的分析，發現暴露單層奈米碳管一週後，體外脾臟T細胞在刀豆素(ConA)刺激下增生能力受到抑制，但在暴露單層奈米碳管兩週及三週T細胞增生並未受到影響。在加入VAG539處理後，發現三種不同型態的樹突細胞(包含CD11c+lowCD11b+MHCII+CD207+ 的蘭格漢氏樹突細胞、CD11c+highCD11b+lowMHCII+CD103+的發炎性CD103+樹突細胞以及CD11c+highCD11b+highMHCII+CD103- 的單核細胞衍生之樹突細胞)以及第二型輔助T細胞、第十七型輔助T細胞以及調節性輔助T細胞於暴露四週時數量顯著下降。羥脯氨酸測試實驗中，發現加入VAG539組別暴露四週時肺部羥脯氨酸含量顯著下降。
　　綜合以上結果，本研究確認了樹突細胞於單層奈米碳管所誘發的肺部纖維化中的貢獻。

To investigate whether dendritic cells regulate the development of single walled carbon nanotube (SWCNT)-induced pulmonary fibrosis. Female C57BL6 mice were oropharyngeally aspirated with 80 μg SWCNT. The results show that CXCL12, CCL2, CCL19, CCL21, IL17, GM-CSF and TGF-β were significantly increased starting at 3 d post exposure to SWCNT. Flow cytometry analyses demonstrate that three different types of dendritic cells infiltrated the lung starting at 3 d, with Langerhans cells-derived dendritic cells (DCs) peaking at 2 wk, and inflammatory CD103+ DCs and monocytes-derived DCs at 4 wk. The number of Th2 in the lungs started to increase at 3 d post exposure to SWCNT, while Th17 and Treg significantly increased starting at 1 wk and peaked at 4 wk. Results ex vivo experiments show that splenic T cells proliferation index was temperaly decreased at 1 wk post exposure. Moreover, treatment with VAG539 attenuated the infiltration of dendritic cells, T cell immune respones and hydroxyproline contents at 4 wk post exposure. These findings indicate that lung DCs modulate SWCNT-induced pulmonary inflammation and fibrosis.

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