Abstract |
TRAIL is known to play a pivotal role in the inhibition of autoimmune disease. We previously demonstrated that administration of dendritic cells engineered to express TRAIL and myelin-oligodendrocyte glycoprotein reduced the severity of experimental autoimmune encephalomyelitis and suggested that CD4(+)CD25(+) regulatory T cells (Tregs) were involved in mediating this preventive effect. In the current study, we investigated the effect of TRAIL on Tregs, as well as conventional T cells, using TRAIL-deficient mice. Upon induction of experimental autoimmune encephalomyelitis, TRAIL-deficient mice showed more severe clinical symptoms, a greater frequency of IFN-γ-producing CD4(+) T (Th1) cells, and a lower frequency of CD4(+)Foxp3(+) Tregs than did wild-type mice. In vitro, conventional T cells stimulated by bone marrow-derived dendritic cells (BM-DCs) from TRAIL-deficient mice showed a greater magnitude of proliferation than did those stimulated by BM-DCs from wild-type mice. In contrast, TRAIL expressed on the stimulator BM-DCs enhanced the proliferative response of CD4(+)CD25(+) Tregs in the culture. The functional TRAILR, mouse death receptor 5 (mDR5), was expressed in conventional T cells and Tregs upon stimulation. In contrast, the decoy receptor, mDc-TRAILR1, was slightly expressed only on CD4(+)CD25(+) Tregs. Therefore, the distinct effects of TRAIL may be due to differences in the mDc-TRAILR1 expression or the signaling pathways downstream of mouse death receptor 5 between the two T cell subsets. Our data suggest that TRAIL suppresses autoimmunity by two mechanisms: the inhibition of Th1 cells and the promotion of Tregs.
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Authors | Tokunori Ikeda, Shinya Hirata, Satoshi Fukushima, Yusuke Matsunaga, Takaaki Ito, Makoto Uchino, Yasuharu Nishimura, Satoru Senju |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 185
Issue 9
Pg. 5259-67
(Nov 01 2010)
ISSN: 1550-6606 [Electronic] United States |
PMID | 20921531
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Receptors, TNF-Related Apoptosis-Inducing Ligand
- TNF-Related Apoptosis-Inducing Ligand
- Tnfrsf10b protein, mouse
- Tnfsf10 protein, mouse
- Tumor Necrosis Factor Decoy Receptors
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Topics |
- Animals
- Autoimmunity
(immunology)
- Cell Proliferation
- Cell Separation
- Encephalomyelitis, Autoimmune, Experimental
(immunology)
- Flow Cytometry
- Immunohistochemistry
- Lymphocyte Activation
(immunology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Receptors, TNF-Related Apoptosis-Inducing Ligand
(immunology)
- Signal Transduction
(immunology)
- T-Lymphocyte Subsets
(immunology)
- T-Lymphocytes, Regulatory
(cytology, immunology)
- TNF-Related Apoptosis-Inducing Ligand
(immunology)
- Th1 Cells
(cytology, immunology)
- Tumor Necrosis Factor Decoy Receptors
(immunology)
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