2011 Fiscal Year Final Research Report
Therapeutic effect of CD28 superagonist on renal disease via expansion of regulatory T cells
| Project/Area Number |
21591030
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ISAKA Yoshitaka 大阪大学, 大学院・医学研究科, 准教授 (00379166)
IMAI Enyu 名古屋大学, 大学院・医学研究科, 特任准教授 (00223305)
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| Project Period (FY) |
2009 – 2011
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| Keywords | CD28 / スーパーアゴニスト / 制御性T細胞 / FoxP3 / 抗GBM抗体腎炎 |
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| Research Abstract |
We hypothesized that a superagonistic monoclonal antibody for CD28, JJ316, which has been known to preferentially expand Treg cells in vivo, could prevent nephrotoxic serum(NTS)-induced nephritis in Wistar-Kyoto rats. Administration of JJ316 attenuated crescent formation, proteinuria, and glomerular accumulation of macrophages and Treg cells. Among glomerular macrophages, the CD163+ subset was significantly increased after treatment, suggesting that Treg cells may modulate the phenotype of macrophages leading to resolution of GN. Adoptive transfer experiment recapitulated the beneficial effects of in vivo administration of JJ316. Furthermore a single injection of JJ316 administered 3 days after disease induction completely protected nephritic rats from death for 2 months. In conclusion, we have demonstrated that treatment with JJ316 has a dramatic therapeutic effect on an experimental crescentic GN, probably due to an expansion of Treg cells.
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Research Products
(6 results)
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[Journal Article] A superagonistic monoclonal antibody for CD28 ameliorates crescentic glomerulonephritis in wistar-kyoto rats2011
Author(s)
Takabatake Y, Li XK, Mizui M, Miyasato K, Matsui I, Kawada N, Imai E, Hunig T, Takahara S, Wada T, Furuichi K, Rakugi H, Isaka Y.
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Journal Title
Mol Med
Volume: 17(7-8)
Pages: 686-96
Peer Reviewed
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[Journal Article] CD28 superagonist-induced regulatory T cell expansion ameliorates mesangioproliferative glomerulonephritis in rats2011
Author(s)
Miyasato K, Takabatake Y, Kaimori J, Kimura T, Kitamura H, Kawachi H, Li XK, Hunig T, Takahara S, Rakugi H, Isaka Y.
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Journal Title
Clin Exp Nephrol
Volume: 15(1)
Pages: 50-7
Peer Reviewed
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