A novel immunotherapy of autoimmune disease by agonistic toll-like receptor 4 antibody
Project/Area Number |
26460058
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Biological pharmacy
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Research Institution | Tohoku University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
TOMIOKA Yoshihisa 東北大学, 大学院薬学研究科, 教授 (00282062)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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Keywords | Toll様受容体 / 自己免疫疾患 / 1型糖尿病 / 免疫寛容 / 機能性抗体 / 抗体医薬 / 自然免疫 / 骨髄由来免疫抑制細胞 / Toll-like receptor / モノクローナル抗体 / 1型糖尿病 / 制御性T細胞 |
Outline of Final Research Achievements |
Type 1 diabetes (T1D) is currently an incurable disease as other most autoimmune diseases. The pathology of T1D progresses from a silent prodromal phase to a clinical phase in which insulin-producing pancreatic β cells is destructed by autoreactive T cells. In this study, we demonstrated that an agonistic monoclonal antibody (mAb) to Toll-like receptor 4 (TLR4) prevents from the onset of T1D by prophylactic treatment and also reverses the new-onset of T1D by therapeutic treatment in nonobese diabetic mice. An agonistic TLR4 mAb induces the tolerance in innate immunity via dendritic cells and myeloid-derived suppressor cells, which results in the suppression of autoimmune T cells. In addition, regulatory T cells are also induced by agonistic TLR4 mAb in both periphery and pancreatic islets. These results propose that a tolerance induction through innate immunity by TLR4 mAb may be a novel immunological approach to cure the autoimmune pathology in T1D.
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] TEX101, a glycoprotein essential for sperm fertility, is required for stable expression of Ly6k on testicular germ cells2016
Author(s)
Endo S, Yoshitake H, Tsukamoto H, Matsuura H, Kato K, Sakuraba M, Takamori K, Fujiwara H, Takeda S, Araki Y
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 23616-23616
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Reversal of New-Onset Type 1 Diabetes With an Agonistic TLR4/MD-2 Monoclonal Antibody2015
Author(s)
Bednar, K.J., Tsukamoto, H., Kachapati, K., Ohta, S., Wu, Y., Katz, J.D., Ascherman, D.P. & Ridgway, W.M.
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Journal Title
Diabetes
Volume: 64
Issue: 10
Pages: 3614-3626
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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