Elucidation of the mechanism of brain tissue-specific regulatory T cell induction
Project/Area Number |
21K19382
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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Research Institution | Kyushu University |
Principal Investigator |
Minako Ito 九州大学, 生体防御医学研究所, 准教授 (70793115)
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Project Period (FY) |
2021-07-09 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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Keywords | 制御性T細胞 / 脳組織Treg |
Outline of Research at the Start |
本研究では脳特異的Tregの誘導機構を明らかにし、全く新しい中枢神経系炎症性疾患の治療・予防法の確立を目指す。①脾臓やリンパ節のTregを脳細胞や脳組織と共培養することによって、Tregに脳特異的な特徴を誘導する脳内因子を明らかにする。②脳梗塞マウスよりTregを単離しTregのT細胞受容体、および脳Tregを活性化させる脳由来抗原を明らかにする。これらを用いて、in vitroで脳Tregを誘導する系を確立する。③マウス生体内で脳Tregの誘導を促進させる、さらに、in vitroで作製した脳Tregを移入することによって、脳内炎症性疾患の治療介入実験を行う。
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Outline of Final Research Achievements |
Naive Tregs derived from spleen were activated and efficiently amplified by T cell receptor (TCR) stimulation in the presence of primary astrocytes. Furthermore, the addition of IL-33 and serotonin was able to confer some of the characteristics of brain Tregs, such as ST2, PPARγ, and serotonin receptor 7 (Htr7) expression. For example, brain Treg markers such as Gata3, Pparg, Il1rl1, Klrg1, Penk, and Htr7 were highly expressed in iB-Tregs. Furthermore, in a Parkinson's disease model, in which T cells are implicated in disease progression, iB-Tregs infiltrated the brain more readily than splenic Tregs and more effectively ameliorated pathological symptoms. These data contribute to our understanding of brain Treg development and indicate that iB-Tregs may be a potential therapeutic agent for inflammatory brain diseases.
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Academic Significance and Societal Importance of the Research Achievements |
制御性T細胞は免疫応答を抑制する細胞であり、様々な炎症性疾患の治療法となりうるが、全身性の免疫抑制のために感染症やがんの拡大などのリスクが高まることが問題として挙げられる。本研究では脳組織に特化したTregを作製することができるため他の組織への影響が少なく、副作用を抑えた治療法につながる。脳に限らず、他の組織の支持細胞や誘導因子と共培養することで、様々な組織特異的なTregの誘導に応用できる可能性がある。
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] Increased neutrophils in inflammatory bowel disease accelerate the accumulation of amyloid plaques in the mouse model of Alzheimer's disease2023
Author(s)
Kaneko R, Matsui A, Watanabe M, Harada Y, Kanamori M, Awata N, Kawazoe M, Takao T, Kobayashi Y, Kikutake C, Suyama M, Saito T, Saido TC, Ito M
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Journal Title
Inflammation and Regeneration
Volume: 43
Issue: 1
Pages: 20-20
DOI
Related Report
Peer Reviewed / Open Access
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