Development of a new treatment for idiopathic pulmonary fibrosis (IPF) by targeting immune receptors
| Project/Area Number |
21K19369
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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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 |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2022: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 免疫システム / 免疫受容体 / 炎症 / 特発性肺線維症 / 分子標的療法 / 免疫関連疾患 / 線維化 |
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| Outline of Research at the Start |
特発性肺線維症 (Idiopathic Pulmonary Fibrosis : IPF) は、原因不明の難治性で進行性の肺線維症であり、診断確定後の平均生存期間は3～5年と極めて予後不良な疾患である。現在、治療薬としては、ピルフェニドンとニンテダニブなどの抗線維化薬があるが、病気の進行を遅らすのみで、治療下でも２年生存率は62％と低い。呼吸苦を伴うことから患者のQOLは極めて悪く、本疾患の克服は社会的なニーズとなっている。
本研究では、IPFの病態に関与する免疫細胞や免疫受容体に着目し、その病態メカニズムを明らかにする。また、IPFの新規分子標的療法開発の可能性を検討する。
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| Outline of Final Research Achievements |
Idiopathic Pulmonary Fibrosis (IPF) is an intractable, progressive pulmonary fibrosis of unknown cause with an extremely poor prognosis, with an average survival of 3 to 5 years after diagnosis is confirmed. Currently, there are anti-fibrotic agents such as pirfenidone and nintedanib as treatments, but they only slow the progression of the disease, and even under treatment, the 2-year survival rate is as low as 62%. Therefore, overcoming this disease has become a social need.
In this study, IPF was induced in mice lacking the gene for the immune receptor DNAM-1 and wild-type mice, and the pathology was significantly reduced in DNAM-1-deficient mice. In addition, when anti-DNAM-1 neutralizing antibodies was administered, the group of mice treated with anti-DNAM-1 neutralizing antibodies showed improvement in disease condition compared to the control group. These results suggest that DNAM-1 is involved in the pathogenesis of IPF.
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| Academic Significance and Societal Importance of the Research Achievements |
特発性肺線維症 (Idiopathic Pulmonary Fibrosis : IPF) は、原因不明の難治性で進行性の肺線維症であり、診断確定後の平均生存期間は3~5年と極めて予後不良な疾患である。現在、治療薬としては、ピルフェニドンとニンテダニブなどの抗線維化薬があるが、病気の進行を遅らすのみで、治療下でも２年生存率は62％と低い。症状も呼吸苦を伴うことから、患者のQOLは極めて悪く、本疾患の克服は社会的なニーズとなっている。
本研究において、私たちは免疫活性化受容体DNAM-1に対する特異抗体がIPF病態を軽減する結果を得た。DNAM-1を標的としたIPF新規治療法の開発が期待される。
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Report
(3 results)
Research Products
(26 results)
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[Journal Article] DNAM-1 regulates Foxp3 expression in regulatory T cells by interfering with TIGIT under inflammatory conditions.2021
Author(s)
Kazuki Sato, Yumi Yamashita-Kanemaru, Fumie Abe, Rikito Murata, Yuho Nakamura-Shinya, Kazumasa Kanemaru, Masafumi Muratani, Andre Veillette, Motohito Goto, Mamoru Ito, Akira Shibuya, Kazuko Shibuya
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Journal Title
Proceedings of the National Academy of Sciences of the United States of America
Volume: 118
Issue: 21
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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