Targeting Siglecs-A novel pharmacological strategy for immuno- and glycotherapy
Targeting Siglecs-A novel pharmacological strategy for immuno- and glycotherapy
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DOI：
10.1016/j.bcp.2011.05.018
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发表时间：
2011-08-15
影响因子：
5.8
通讯作者：
von Gunten, Stephan
中科院分区：
文献类型：
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作者：
Jandus, Camilla;Simon, Hans-Uwe;von Gunten, Stephan
免疫系统必须严格控制，以避免旁观者组织损伤以及由压倒性免疫反应引起的自身反应。一个新的免疫调节，碳水化合物结合受体家族，Siglecs（唾液酸结合免疫球蛋白样凝集素），由于其介导细胞死亡，抗增殖作用和调节各种细胞活动的能力而受到特别关注。Siglec受体主要以细胞类型特异性和分化依赖性的方式在白细胞上表达。Siglecs可能潜在地被利用作为新的免疫和糖疗法的靶点，用于自身免疫性和过敏性疾病以及血液恶性肿瘤的细胞导向治疗。在这里，我们提出了关于Siglecs及其配体的结构和功能特征、表达模式和进化方面的新见解。讨论了使用Siglec激动性交联疗法的药理学策略，如单克隆或工程抗体，静脉注射免疫球蛋白（IVIG）或糖仿制品。利用激动剂或拮抗剂靶向Siglecs来调节免疫应答可能具有重要的临床意义，并可能为自身免疫性和过敏性疾病的治疗或肿瘤免疫治疗开辟新的药理学途径。(C) 2011爱思唯尔公司版权所有。
The immune system must be tightly held in check to avoid bystander tissue damage as well as autoreactivity caused by overwhelming immune reactions. A novel family of immunoregulatory, carbohydrate-binding receptors, the Siglecs (sialic acid binding immunoglobulin-like lectins), has received particular attention in light of their capacity to mediate cell death, anti-proliferative effects and to regulate a variety of cellular activities. Siglec receptors are mainly expressed on leukocytes in a cell type-specific and differentiation-dependent manner. Siglecs might potentially be exploited as targets of novel immune- and glycotherapeutics for cell-directed therapies in autoimmune and allergic diseases, as well as in haematologic malignancies. Here we present novel insights on structural and functional characteristics, expression patterns and evolutionary aspects of Siglecs and their ligands. Pharmacological strategies using Siglec agonistic cross-linking therapeutics, such as monoclonal or engineered antibodies, intravenous immunoglobulin (IVIG), or glycomimetics are discussed. Modulation of immune responses by targeting Siglecs using agonistic or antagonistic therapeutics may have important clinical implications and may pave the way for novel pharmacological avenues for the treatment of autoimmune and allergic diseases or for tumor immunotherapy. (C) 2011 Elsevier Inc. All rights reserved.