密歇根大学医学系外科免疫疗法分部，中国中科院生物物理研究所联合研究的新成果在Science的在线版发布，主要解析了CD24与Siglec-10对免疫应答的选择性抑制作用。
生物世界中的受体识别模式具有区分病原或是损伤细胞的成分的功能，通常受损伤的细胞如不被清除可能对机体有危害，受体识别可能激活天然免疫系统。值得关注的一点是，机体如何通过受体识别机制来区分外源病原和自身损伤细胞，个中的分子机制一直鲜为人知。
在本篇Science研究性文章中，研究人员发现，CD24缺乏的生物模型小鼠表现出对自身损伤细胞成分更敏感，而对外源性病原没有出现异常，于是研究小组对这一分子机制开展研究。
研究发现CD24与高迁移率族蛋白B1(high-mobility group box-1,HMGB1，HMGB1是一种DNA结合蛋白,可作为细胞因子参与炎症反应)，热休克蛋白70（Heat shock protein70，HSP70），热休克蛋白90（heat shock protein 90，HSP90）具有功能上的联系。CD24是HMGB1，HSP70，HSP90蛋白的负调控因子，它能降低这些蛋白的活性，还能抑制核因子κB（nuclear factor-kappa B，NF-κB）的活性。在生物模型小鼠的研究中发现这一负调控功能的实现很大程度上依赖Siglec-10或Siglec-G。
这些研究结果显示CD24-Siglec-G通路具有保护宿主的功能，它通过负调节机制降低宿主对病理性的细胞死亡成分的致死性天然免疫应答活性，保护宿主免受自体免疫性的伤害，通过这一模式来区分免疫原来自本身还是来自外界。（生物谷Bioon.com）
生物谷推荐原始出处：
Science DOI: 10.1126/science.1168988
CD24 and Siglec-10 Selectively Repress Tissue Damage–Induced Immune Responses
Guo-Yun Chen 1, Jie Tang 2, Pan Zheng 3*, Yang Liu 4*
1 Division of Immunotherapy, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
2 Institute of Biophysics, Chinese Academy of Science, Beijing, China.
3 Division of Immunotherapy, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.; Division of Immunotherapy, Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
4 Division of Immunotherapy, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.; Division of Immunotherapy, Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Patten recognition receptors, which recognize pathogens or components of injured cells (danger), trigger activation of the innate immune system. Whether and how the host distinguishes between danger- versus pathogen-associated molecular patterns remains unresolved. We report that CD24-deficient mice exhibit increased susceptibility to danger- but not pathogen-associated molecular patterns. CD24 associates with high mobility group box 1 (HMGB1), heat shock protein 70 (HSP70), and heat shock protein 90 (HSP90), negatively regulates their stimulatory activity, and inhibits nuclear factor-kappa B (NF-B) activation. This occurs at least in part through CD24 association with Siglec-10 in humans or Siglec-G in mice. Our results reveal that the CD24-Siglec-G pathway protects the host against a lethal response to pathological cell death and discriminates danger- versus pathogen-associated molecular patterns.
