| Item type |
文献 / Documents(1) |
| 公開日 |
2017-12-28 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1371/journal.pone.0048798 |
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関連名称 |
10.1371/journal.pone.0048798 |
| 出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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タイトル |
Fas-Independent T-Cell Apoptosis by Dendritic Cells Controls Autoimmune Arthritis in MRL/lpr Mice |
| 著者 |
井澤, 俊
近藤, 智之
クロサワ, ミエ
大浦, 律子
松本, 一真
田中, 栄二
山田, 安希子
新垣, 理恵子
工藤, 保誠
林, 良夫
石丸, 直澄
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| 抄録 |
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内容記述 |
Background: Although autoimmunity in MRL/lpr mice occurs due to a defect in Fas-mediated cell death of T cells, the role of Fas-independent apoptosis in pathogenesis has rarely been investigated. We have recently reported that receptor activator of nuclear factor (NF)-kB ligand (RANKL)-activated dendritic cells (DCs) play a key role in the pathogenesis of rheumatoid arthritis (RA) in MRL/lpr mice. We here attempted to establish a new therapeutic strategy with RANKL-activated DCs in RA by controlling apoptosis of peripheral T cells. Repeated transfer of RANKL-activated DCs into MRL/lpr mice was tested to determine whether this had a therapeutic effect on autoimmunity.
Methods and Finding: Cellular and molecular mechanisms of Fas-independent apoptosis of T cells induced by the DCs were investigated by in vitro and in vivo analyses. We demonstrated that repeated transfers of RANKL-activated DCs into MRL/lpr mice resulted in therapeutic effects on RA lesions and lymphoproliferation due to declines of CD4+ T, B, and CD4‾CD8‾ double negative (DN) T cells. We also found that the Fas-independent T-cell apoptosis was induced by a direct interaction between tumor necrosis factor (TNF)-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) on T cells and TRAIL on Fas-deficient DCs in MRL/lpr mice.
Conclusion: These results strongly suggest that a novel Fas-independent apoptosis pathway in T cells maintains peripheral tolerance and thus controls autoimmunity in MRL/lpr mice. |
| 書誌情報 |
en : PLOS ONE
巻 7,
号 12,
p. e48798,
発行日 2012-12-12
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
19326203 |
| 出版者 |
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出版者 |
PLOS |
| 権利情報 |
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|
権利情報 |
Copyright: © 2012 Izawa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| EID |
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識別子 |
258924 |
| 言語 |
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|
言語 |
eng |
pone_7_12_e48798.pdf (1.33 MB)
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