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The immunoregulatory effect of tumor necrosis factor-related apoptosis inducing ligand (TRAIL)
Bibliographic Information
- Title
- The immunoregulatory effect of tumor necrosis factor-related apoptosis inducing ligand (TRAIL)
- Other Title
-
- 免疫抑制分子TRAILによる自己免疫疾患の制御機構に関する研究
- メンエキ セイギョ ブンシ TRAIL ニ ヨル ジコ メンエキ シッカン ノ セイギョ キコウ ニ カンスル ケンキュウ
- Author
- 池田, 徳典
- Author
- Ikeda, Tokunori
- University
- 熊本大学
- Types of degree
- 博士 (医学)
- Grant ID
- 甲第1771号
- Degree year
- 2011-03-25
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Description
type:学位論文(Thesis)
Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is known to play a pivotal role in the inhibition of autoimmune disease. We previously reported a disease-preventive effect of embryonic stem cell-derived dendritic cells (ES-DC) genetically engineered to express TRAIL along with a myelin antigen, MOG, on experimental autoimmune encephalomyelitis (EAE), and also suggested that CD4+CD25+ regulatory T (Treg) cells were involved in mediating this preventive effect. In the current study, we investigated the effect of TRAIL on Treg cells as well as conventional T cells, using TRAIL-deficient mice. Upon induction of EAE, TRAIL-deficient mice showed more severe clinical symptoms, a higher frequency of IFN-γ-producing CD4+ T (Th1) cells, and a lower frequency of CD4+Foxp3+ Treg cells than wild type mice. In vitro, conventional T cells stimulated by bone marrow-derived DC (BM-DC) from TRAIL-deficient mice showed a higher magnitude of proliferation than those stimulated by BM-DC from wild type mice. In contrast, TRAIL expressed on the stimulator BM-DC enhanced the proliferative response of CD4+CD25+ Treg cells in the culture. The functional TRAIL-receptor, mDR5, was expressed in both conventional T cells and Treg cells upon stimulation. On the other hand, the decoy receptor, mDc-TRAIL-R1 was slightly expressed only on CD4+CD25+ Treg cells. Therefore, the distinct effects of TRAIL may be due to differences in the mDc-TRAIL-R1-expreesion or the signaling pathways down-stream of mDR5 between the two T cell subsets. Our data suggests that TRAIL suppresses autoimmunity by two mechanisms; one is the inhibition of Th1 cells and the other is the promotion of Treg cells.
博士論文