Elucidation of the pathology of SLE by TLR7 regulation and development of novel antibody therapeutics.

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K08892
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Juntendo University
• Principal Investigator: Hirofumi Amano 順天堂大学, 医学部, 先任准教授 (50318474)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 全身性エリテマトーデス / TLR７ / 新規治療

Outline of Final Research Achievements

We confirmed the expression of TLR7 in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) was higher in the myeloid cell population compared with healthy control. Furthermore, the expression was observed not only within the cells but also on the cell surface. We also analyzed the expression of soluble TLR7 in SLE patient serum using SLE patient serum. The expression was lower in the serum of SLE patients than in healthy subjects. When we conducted research using anti-TLR7 antibody administration to SLE model mice, we confirmed that nephritis was significantly suppressed and survival rate was markedly prolonged. We can expect that anti-human TLR7 antibodies will be used as new therapeutic agents and show efficacy in the future.

Free Research Field

自己免疫疾患の制御

Academic Significance and Societal Importance of the Research Achievements

全身性エリテマトーデス(SLE)患者の病態において、TLR7の重要性はよく知られている。われわれは、複数のモノクローナル抗体を用いることで、より特異性の高い抗TLR７を同定し、患者末梢血における発現を調べた。その発現は、自然免疫に重要な好中球や単球の細胞質のみならず、細胞表面にも発現を確認できたことは、抗体治療薬の有効性を示唆するものである。SLEのモデルマウスに対する抗TLR7抗体投与により、腎炎を著明に抑制し、生存率を延長させたことから、今後抗ヒトTLR7抗体が新規治療薬として使用され有効性を示す可能性が期待できる。