Development of a new treatment for idiopathic pulmonary fibrosis (IPF) by targeting immune receptors

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19369
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: University of Tsukuba
• Principal Investigator: Shibuya Kazuko 筑波大学, 医学医療系, 教授 (00302406)
• Project Period (FY): 2021-07-09 – 2023-03-31
• 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

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.

Free Research Field

免疫学

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。