Lgals9 deficiency attenuates nephritis and arthritis in lupus model

• Project/Area Number: 17K09976
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Okayama University
• Principal Investigator: Kawabata Tomoko 岡山大学, 医学部, 客員研究員 (90600669)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: SLE / ガレクチン9 / ガレクチン９ / 全身性エリテマトーデス

Outline of Final Research Achievements

Galectin 9 (Gal-9, Lgals9) is a b-galactoside-binding lectin that has been used for clinical application in autoimmune diseases. This study was undertaken to investigate whether deficiency of Lgals9 has beneficial or deleterious effects on lupus in a murine model.Lgals9 deficiency protected against the development of immune complex glomerulonephritis,arthritis, and peritoneal lipogranuloma formation in BALB/c mice in this murine model of pristane-induced lupus. Furthermore, Lgals9 deficiency protected against pristane-induced lupus without altering the Toll-like receptor type I interferon pathway.Gal-9 is required for the induction and development of lupus nephritis and arthritis in this murine model of SLE. The results of the current investigation provide a potential new strategy in which antagonism of Gal-9 may be beneficial for the treatment of nephritis and arthritis in patients with SLE through targeting of activated macrophages.

Academic Significance and Societal Importance of the Research Achievements

ガレクチン-9 (Galectin 9; Gal-9)は我々が最初に発見した分子であり、免疫関連組織や細胞を含む種々の臓器に広く発現している。全身性エリテマトーデス（SLE）をはじめとした自己免疫疾患への治療応用を念頭においた病態解明が求められるが、未だ不明な点も多い。しかし本研究では誘発系疾患モデルであるGal欠損マウスに対してプリスタン投与を行った結果、関節炎や腎症の活動性が低下、またlipogranulomaの形成が抑制された。Gal-9の拮抗は活性化マクロファージを介して、SLE腎症や関節炎の治療に効果ある可能性を示唆した。

Research Products

• [Journal Article] Lgals9 deficiency attenuates nephritis and arthritis in pristane-induced lupus model of BALB/c mice (2018)
  • Author(s): Zeggar S, Watanabe KS, Teshigawara S, Hiramatsu S, Katsuyama T, Katsuyama E, Watanabe H, Matsumoto Y, Kawabata T, Sada KE, Niki T, Hirashima M, Wada J.
  • Journal Title: Arthritis Rheumatol. Volume: - Issue: 7 Pages: 1089-1101
  • DOI: 10.1002/art.40467
  • Peer Reviewed / Open Access