探討zymosan合併IL-10對樹突細胞的調節與對OVA致敏氣喘小鼠的影響

Zymosan為酵母菌菌壁上的一種衍生物，已有許多研究指出，zymosan可透過與樹突細胞的TLR-2及dectin-1的結合作用，刺激樹突細胞表現較多量的細胞激素IL-10生成。另外，IL-10已知可應用於抑制Th1與Th2的細胞反應。因此，在本研究我們進一步評估zymosan合併帶有IL-10腺病毒載體 (Ad-IL-10) 作用下的樹突細胞的特性以及其應用在預防過敏氣喘疾病上的可行性。在細胞實驗上發現，合併給予zymosan與Ad-IL-10刺激會促使樹突狀細胞的MHCⅡ表現下降，但共同刺激分子CD80有明顯上升的現象。另一方面，若將合併刺激後的樹突細胞和T細胞共培養後，會抑制Th2細胞的生成，並促進Th1細胞的分化。此外，在共同培養下，T細胞群的增生能力降低。另外，我們進一步將單獨或合併給予zymosan與Ad-IL-10作用的樹突細胞送入老鼠體內，於此氣喘動物模式觀察小鼠過敏氣喘的反應。結果顯示，單獨給予Ad-IL-10可以有效抑制OVA專一性IgE抗體的生成、嗜酸性白血球的聚集，以及降低肺中發炎物質與Th2細胞激素的表現。而給予合併作用後的樹突細胞雖也有抑制效果，但較不明顯。綜合以上結果，合併給予zymosan和Ad-IL-10的樹突細胞雖然可能可以抑制Th2的反應生成，但這種修飾後的樹突細胞並不適用在預防過敏疾病上，因此，將來是否可利用此種樹突細胞來進行對過敏氣喘疾病的治療，仍需更進一步的確認。

關鍵字

樹突細胞

並列摘要

Zymosan, a yeast cell wall derivative, can stimulate dendritic cells to secrete abundant IL-10. Zymosan is also known to induce IFN-γ producing Th1 cells. Otherwise, Interleukin-10 (IL-10), a known suppressive cytokine, can inhibit antigen-specific proliferation of CD4+T cells regardless of the subset (Th1 or Th2).In this study, the immuno-modulatory effects of IL-10 and zymosan on dendritic cells (DCs) and their potential preventive effects against ovalbumin (OVA)-induced asthma were investigated. Firstly, we applied Ad-IL-10 and zymosan to treat the bone marrow derived dendritic cells and found that such modified DCs expressed increased levels of CD80 and decreased levels of MHC II. In addition, the data demonstrated that DCs treated with zymosan plus Ad-IL-10 induced CD4+T cells to differentiate to Th1 cells but not Th2 cells. Further, Ad-IL-10 and zymosan-modified DCs could reduced the proliferation of antigen-specific T cells. In animal experiments, we showed that these modified DCs efficiently inhibited the airway eosinophilia and Th2 responses. Our data also showed that combined treatment significantly enhanced the production of IL-10 in the lungs. However, the preventive effects of these modified DCs in the development of airway hyper-responsiveness and airway inflammation were not obvious compared with Ad-IL-10-infected DCs. Thus, we propose that Ad-IL-10 but not zymosan expressed a more inhibitory effects on Th2 immune responses in asthmatic mice. Taken together, although these data demonstrated that these modified DCs may not be an efficient tool in application of prevention for allergic diseases, it is possible to be used for therapy in the future.

並列關鍵字

zymosan ； IL-10 ； dendritic cells

參考文獻

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探討zymosan合併IL-10對樹突細胞的調節與對OVA致敏氣喘小鼠的影響

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