Introduction to special Issue: Emerging Roles of Siglecs in Health and Disease
Introduction to special Issue: Emerging Roles of Siglecs in Health and Disease
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特刊简介：Siglecs 在健康和疾病中的新兴作用
DOI：
10.1093/glycob/cwu073
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发表时间：
2014
期刊：
影响因子：
4.3
通讯作者：
P. R. et al.
中科院分区：
文献类型：
--
作者：
Crocker;P. R. et al.
自唾液酸结合Ig样凝集素的Siglec家族被发现以来的20年中（Kelm等人，1994），重要的目标是理解这些蛋白质在表达它们的造血、免疫和神经系统的背景下的生物学功能。在这一系列的五篇综述中，讨论了siglecs在各种疾病中的作用，包括炎症，神经变性，自身免疫和传染病。在第一篇综述中，Angata概述了人类siglec多态性及其与疾病的关系。特别令人感兴趣的是新出现的数据，表明小胶质细胞（脑巨噬细胞）上的⑶ 33/Siglec-3的表达与晚发性阿尔茨海默病相关。Neumann及其同事的综述描述了小胶质细胞表达的其他抑制性siglecs，如Siglec-11，如何抑制细胞活化并防止神经毒性。Chen及其同事强调了siglecs在调节炎症反应中的重要性。他们描述了由B细胞和树突状细胞表达的Siglec-G通过与高度唾液酸化的蛋白质CD 24的顺式相互作用在抑制无菌炎症中的作用，CD 24是HMGB 1和热休克蛋白等“炎症相关分子模式”的重要受体。B细胞是驱动许多自身免疫性疾病如系统性红斑狼疮的关键，它们对“自身”抗原的反应受到严格控制。Nitschke的综述描述了主要的B细胞单克隆抗体CD 22（Siglec-2）和Siglec-G的最新进展，以及它们如何差异调节B细胞亚群的激活并帮助维持B细胞耐受性。虽然上述文章集中在siglecs在介导唾液酸依赖性与宿主细胞相互作用中的作用，但Chang和Nizet的最后综述讨论了各种病原体呈递的唾液酸如何能够与siglecs相互作用并调节宿主反应。一方面，与巨噬细胞受体唾液酸粘附素（Siglec-1）的相互作用可以通过触发病原体清除和细胞因子产生来促进宿主防御功能。另一方面，病原体参与抑制性信号分子如Siglec-E对巨噬细胞和嗜中性粒细胞的作用可以抑制宿主免疫应答并有利于病原体存活。总的来说，这一系列的评论提供了一个及时的总结，我们已经走了多远，在我们的siglec生物学的理解，因为最初发现的唾液酸粘附素作为巨噬细胞血凝素。
Over the 20 years since the Siglec family of sialic acid binding Ig-like lectins was discovered (Kelm et al. 1994), an important goal has been to understand the biological functions of these proteins in the context of the hematopoietic, immune and nervous systems where they are expressed. In this series of five reviews, the roles of siglecs in a variety of disease scenarios are addressed, including inflammation, neurodegeneration, autoimmunity and infectious disease. In the first review, Angata provides an overview of human siglec polymorphisms and their associations with disease. Of particular interest are emerging data indicating that the expression of CD33/Siglec-3 on microglia (brain macrophages) is associated with late onset Alzheimer’s disease. The review by Neumann and colleagues describes how other inhibitory siglecs expressed by microglia, such as Siglec-11, dampen cellular activation and prevent neurotoxicity. The importance of siglecs in regulating inflammatory responses is highlighted by Chen and colleagues. They describe the role of Siglec-G expressed by B cells and dendritic cells in dampening sterile inflammation via cis-interactions with the heavily sialylated protein, CD24, an important receptor for ‘danger-associated molecular patterns’ such as HMGB1 and heat shock proteins. B cells are key in driving many autoimmune disease such as systemic lupus erythematosus and their responses to ‘self’-antigens are under tight control. The review by Nitschke describes recent progress on the major B-cell siglecs, CD22 (Siglec-2) and Siglec-G, and how they differentially regulate activation of B-cell subsets and help maintain B-cell tolerance. While the above articles focus on the role of siglecs in mediating sialic acid-dependent interactions with host cells, the final review by Chang and Nizet discusses how sialic acids presented by various pathogens are able to interact with siglecs and modulate host responses. On the one hand, interactions with the macrophage receptor sialoadhesin (Siglec-1) may promote host defence functions by triggering pathogen clearance and cytokine production. On the other hand, pathogen engagement of inhibitory siglecs such as Siglec-E on macrophages and neutrophils can suppress host immune responses and favor pathogen survival. Taken together, this series of reviews provides a timely summary of how far we have come in our understanding of siglec biology since the original discovery of sialoadhesin as a macrophage hemagglutinin.