Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in non-obese diabetic mice: From regulatory mechanism to clinical implication
博士 === 國防醫學院 === 生命科學研究所 === 92 === To investigate the regulatory effects of decoy receptor 3 (DcR3) on the differentiation and function of dendritic cells (DCs), bone marrow-derived DCs from non-obese diabetic (NOD) mice were cultured with recombinant DcR3.Fc protein and their differentiating pheno...
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ndltd-TW-092NDMC01050102016-06-17T04:16:18Z http://ndltd.ncl.edu.tw/handle/47602600741373620569 Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in non-obese diabetic mice: From regulatory mechanism to clinical implication 第三號誘餌受體蛋白質對非肥胖型糖尿病小鼠骨髓樹突狀細胞之免疫調控作用:從免疫機轉到疾病運用 Shu-Fen Wu 吳淑芬 博士 國防醫學院 生命科學研究所 92 To investigate the regulatory effects of decoy receptor 3 (DcR3) on the differentiation and function of dendritic cells (DCs), bone marrow-derived DCs from non-obese diabetic (NOD) mice were cultured with recombinant DcR3.Fc protein and their differentiating phenotypes and T cell-stimulating functions were then evaluated. Compared to DCs incubated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4), the expressions of CD11c, CD40, CD54 and MHC I-Ag7 were decreased on cells cultured with additional DcR3.Fc, indicating DcR3 can interfere with the differentiation and maturation of bone marrow-derived DCs. One of the most striking effects of DcR3.Fc on DC’s differentiation was the up-regulation of CD86 and down-regulation of CD80, suggesting the modulatory potential to skew T cell response toward the Th2 phenotype. In consistent with this, the proliferation of CD4+ T cells co-cultured with DcR3.Fc-treated DCs was significant decreased, compared to that of T cells stimulated by regular DCs. Moreover, the secretion of IFN-g from T cells co-cultured with DcR3.Fc-treated DCs was profoundly suppressed, indicating a Th1-suppressing effect of DcR3 on differentiating DCs. Data from two-dimensional gel electrophoresis and MALDI-TOF analysis showed up-regulation of some proteins, such as mitogen-activated protein kinase p38 beta, cyclin-dependent kinase 6, and signal-induced proliferation associated gene 1, and down-regulation of interleukin-17 precursor, TANK-binding kinase 1, and golgi SNAP in cells treated with DcR3, further indicating its effect on DC differentiation and function. In summary, our results indicate DcR3 may act not only as a decoy receptor to its known ligands, but also as an effector molecule to modulate the differentiation and function of DCs and thus down-regulate the Th1 immune response. This modulatory effect of DcR3 to restore and/or enhance the Th2 immune response in NOD mice may provide the basis for future theraputic application on autoimmune diabetes. Heuy-Kang Sytwu 司徒惠康 2003 學位論文 ; thesis 94 zh-TW |
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博士 === 國防醫學院 === 生命科學研究所 === 92 === To investigate the regulatory effects of decoy receptor 3 (DcR3) on the differentiation and function of dendritic cells (DCs), bone marrow-derived DCs from non-obese diabetic (NOD) mice were cultured with recombinant DcR3.Fc protein and their differentiating phenotypes and T cell-stimulating functions were then evaluated. Compared to DCs incubated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4), the expressions of CD11c, CD40, CD54 and MHC I-Ag7 were decreased on cells cultured with additional DcR3.Fc, indicating DcR3 can interfere with the differentiation and maturation of bone marrow-derived DCs. One of the most striking effects of DcR3.Fc on DC’s differentiation was the up-regulation of CD86 and down-regulation of CD80, suggesting the modulatory potential to skew T cell response toward the Th2 phenotype. In consistent with this, the proliferation of CD4+ T cells co-cultured with DcR3.Fc-treated DCs was significant decreased, compared to that of T cells stimulated by regular DCs. Moreover, the secretion of IFN-g from T cells co-cultured with DcR3.Fc-treated DCs was profoundly suppressed, indicating a Th1-suppressing effect of DcR3 on differentiating DCs. Data from two-dimensional gel electrophoresis and MALDI-TOF analysis showed up-regulation of some proteins, such as mitogen-activated protein kinase p38 beta, cyclin-dependent kinase 6, and signal-induced proliferation associated gene 1, and down-regulation of interleukin-17 precursor, TANK-binding kinase 1, and golgi SNAP in cells treated with DcR3, further indicating its effect on DC differentiation and function. In summary, our results indicate DcR3 may act not only as a decoy receptor to its known ligands, but also as an effector molecule to modulate the differentiation and function of DCs and thus down-regulate the Th1 immune response. This modulatory effect of DcR3 to restore and/or enhance the Th2 immune response in NOD mice may provide the basis for future theraputic application on autoimmune diabetes.
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author2 |
Heuy-Kang Sytwu |
author_facet |
Heuy-Kang Sytwu Shu-Fen Wu 吳淑芬 |
author |
Shu-Fen Wu 吳淑芬 |
spellingShingle |
Shu-Fen Wu 吳淑芬 Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in non-obese diabetic mice: From regulatory mechanism to clinical implication |
author_sort |
Shu-Fen Wu |
title |
Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in non-obese diabetic mice: From regulatory mechanism to clinical implication |
title_short |
Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in non-obese diabetic mice: From regulatory mechanism to clinical implication |
title_full |
Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in non-obese diabetic mice: From regulatory mechanism to clinical implication |
title_fullStr |
Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in non-obese diabetic mice: From regulatory mechanism to clinical implication |
title_full_unstemmed |
Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in non-obese diabetic mice: From regulatory mechanism to clinical implication |
title_sort |
immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in non-obese diabetic mice: from regulatory mechanism to clinical implication |
publishDate |
2003 |
url |
http://ndltd.ncl.edu.tw/handle/47602600741373620569 |
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