Department of Surgery, Surgical Research Laboratories, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Med Res Rev. 2013 Jun;33 Suppl 1:E102-26. doi: 10.1002/med.20249. Epub 2011 Jul 26.
In recent years, an important role has emerged for the glycan-binding protein Galectin-9 (Gal-9) in health and disease. In normal physiology, Gal-9 seems to be a pivotal modulator of T-cell immunity by inducing apoptosis in specific T-cell subpopulations. Because these T-cell populations are associated with autoimmunity, inflammatory disease, and graft rejection, it was postulated that application of exogenous Gal-9 may limit pathogenic T-cell activity. Indeed, treatment with recombinant Gal-9 ameliorates disease activity in various preclinical models of autoimmunity and allograft graft rejection. In many solid cancers, the loss of Gal-9 expression is closely associated with metastatic progression. In line with this observation, treatment with recombinant Gal-9 prevents metastatic spread in various preclinical cancer models. In addition, various hematological malignancies are sensitive to apoptotic elimination by recombinant Gal-9. Here, we review the biology and physiological role of this versatile lectin and discuss the therapeutic potential of Gal-9 in various diseases, including autoimmunity, asthma, infection, and cancer.
近年来,糖结合蛋白半乳糖凝集素-9(Galectin-9,Gal-9)在健康和疾病中的作用变得非常重要。在正常生理状态下,Gal-9 通过诱导特定 T 细胞亚群凋亡,似乎成为 T 细胞免疫的关键调节剂。由于这些 T 细胞群与自身免疫、炎症性疾病和移植物排斥有关,因此推测外源性 Gal-9 的应用可能限制致病性 T 细胞的活性。事实上,重组 Gal-9 的治疗可改善各种自身免疫和同种异体移植物排斥的临床前模型中的疾病活动。在许多实体瘤中,Gal-9 表达的缺失与转移进展密切相关。与此观察结果一致,重组 Gal-9 的治疗可预防各种临床前癌症模型中的转移扩散。此外,各种血液系统恶性肿瘤对重组 Gal-9 的凋亡消除敏感。在这里,我们回顾了这种多功能凝集素的生物学和生理作用,并讨论了 Gal-9 在包括自身免疫、哮喘、感染和癌症在内的各种疾病中的治疗潜力。