- 學位論文
探討前列腺素I2對樹突細胞之 免疫調節作用
Study on the Modulatory Effect of Prostaglandin I2 on Dendritic Cells
摘要
前言:前列腺素I2(PGI2)在臨床上已廣泛應用於治療血管疾病。近 幾年才有研究發現PGI2具有抗發炎的作用，並可藉由透過樹突細胞上 的PGI2接受器來達到免疫調節的能力。而樹突細胞具有啟動免疫系統 及藉由誘發調節性T細胞來達到免疫耐受性的功能。然而PGI2是否藉 由調控樹突細胞來影響CD4+ T細胞的分化，進而達到免疫調節作用目 前還並不清楚。 實驗方法:以PGI2 analog(iloprost)處理第八天骨髓樹突細胞，同時 給予LPS當作刺激因子，分析樹突細胞分泌細胞激素的情形，且觀察 iloprost對於樹突細胞的成熟度以及刺激T細胞增生能力的影響，再進一步分析對於調節性T細胞的影響。 結果:在LPS的存在下，iloprost可以有效增加樹突細胞分泌抗發炎的 細胞激素IL-10，並且抑制促進發炎的細胞激素IL-12、IL-6、IL-23及TNF-a，但不影響TGF-b的表現量。在成熟度方面，LPS所引起的成 熟作用被iloprost抑制，減少MHC class II，CD86及CD40的表現量， 但不影響CD80的表現。經iloprost處理後的樹突細胞可抑制CD4+ T細 胞增生的能力，且增加抗原特異性CD4+ T細胞分泌的IL-10，另一方 面，會抑制naïve T細胞分化成Th1及Th2的CD4+ T細胞的比例。此外，經iloprost處理後的樹突細胞會增加naïve T細胞轉變成調節性T細胞的能力(Treg differentiation)，但不影響調節性T細胞的增生。 結論:我們證實了iloprost可以讓樹突細胞轉變成耐受性樹突細胞，並且可增加Treg differentiation的能力，而這些研究可進一步幫助了解耐受性樹突細胞的功能，並作為發炎性疾病治療的參考。
並列摘要
Background:PGI2 has anti-inflammatory effect and modulate the immune responses mediated by dendritic cells through prostaglandin I2 receptor (IP). Dendritic cells (DCs) play important roles in innate and adaptive immune responses. DCs also can induce immune tolerance by modulating regulatory T cells (Treg) function and differentiation. However, whether PGI2-modulated DCs affect CD4+ T cells differentiation is still not clear. Methods:Murine bone-marrow derived DCs (BMDCs) were treated with PGI2 analog, iloprost, in the presence of LPS for 24 hour. We analyzed cytokine production and phenotype expression of iloprost-treated BMDCs. We next examined the effect of iloprost-treated BMDCs on T cell function, Treg cell differentiation and expansion. Results:Our data showed that iloprost inhibited proinflammatory cytokine (IL-12, IL-6, IL-23, TNF-a) production and increased anti-inflammatory cytokine IL-10 secretion from BMDCs in response to LPS. However, iloprost did not change the TGF-b expression of BMDCs. Furthermore, iloprost-treated BMDCs displayed immature phenotype with low expression of MHC class II, CD86 and CD40. In addition, iloprost-treated BMDCs inhibited Ag-specific CD4+ T cells proliferation, Th1 and Th2 differentiation and promoted Treg cell development from naïve T cells in vitro. Conclusions:Our study demonstrated that iloprost-modulated BMDCs exhibited tolerogenic properties in vitro. This study will help us to explore strategies to design cell therapy for patients with autoimmune diseases, such as systemic lupus erythematosus (SLE).