密歇根大學(xué)醫(yī)學(xué)系外科免疫療法分部,，中國(guó)中科院生物物理研究所聯(lián)合研究的新成果在Science的在線版發(fā)布，主要解析了CD24與Siglec-10對(duì)免疫應(yīng)答的選擇性抑制作用,。
生物世界中的受體識(shí)別模式具有區(qū)分病原或是損傷細(xì)胞的成分的功能，通常受損傷的細(xì)胞如不被清除可能對(duì)機(jī)體有危害,，受體識(shí)別可能激活天然免疫系統(tǒng),。值得關(guān)注的一點(diǎn)是，機(jī)體如何通過(guò)受體識(shí)別機(jī)制來(lái)區(qū)分外源病原和自身?yè)p傷細(xì)胞,，個(gè)中的分子機(jī)制一直鮮為人知,。
在本篇Science研究性文章中，研究人員發(fā)現(xiàn),，CD24缺乏的生物模型小鼠表現(xiàn)出對(duì)自身?yè)p傷細(xì)胞成分更敏感,，而對(duì)外源性病原沒(méi)有出現(xiàn)異常，于是研究小組對(duì)這一分子機(jī)制開(kāi)展研究,。
研究發(fā)現(xiàn)CD24與高遷移率族蛋白B1(high-mobility group box-1,HMGB1,，HMGB1是一種DNA結(jié)合蛋白,可作為細(xì)胞因子參與炎癥反應(yīng))，熱休克蛋白70（Heat shock protein70,，HSP70）,，熱休克蛋白90（heat shock protein 90，HSP90）具有功能上的聯(lián)系,。CD24是HMGB1,，HSP70，HSP90蛋白的負(fù)調(diào)控因子,，它能降低這些蛋白的活性,，還能抑制核因子κB（nuclear factor-kappa B，NF-κB）的活性,。在生物模型小鼠的研究中發(fā)現(xiàn)這一負(fù)調(diào)控功能的實(shí)現(xiàn)很大程度上依賴Siglec-10或Siglec-G,。
這些研究結(jié)果顯示CD24-Siglec-G通路具有保護(hù)宿主的功能，它通過(guò)負(fù)調(diào)節(jié)機(jī)制降低宿主對(duì)病理性的細(xì)胞死亡成分的致死性天然免疫應(yīng)答活性,，保護(hù)宿主免受自體免疫性的傷害,，通過(guò)這一模式來(lái)區(qū)分免疫原來(lái)自本身還是來(lái)自外界。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
