CD24分子是一种具有免疫调节作用的糖基化磷脂酰肌醇锚定分子，其免疫调节机制尚不清楚。我们发现：anti-CD24中和抗体能加重野生型小鼠肝损伤，表现为小鼠死亡率升高、肝出血、谷丙转氨酶等肝功能指标以及血清中TNF-α明显增加，利用CD24-/-小鼠进一步证实了该结果。利用Rag1-/-小鼠，重复上述实验发现小鼠的各项指标无明显改变。我们假设：CD24分子可能是急性肝损伤的一个重要负反馈调节分子，在肝脏中某种或几种固有免疫细胞上表达，通过调节固有免疫反应抑制肝内炎症反应和肝损伤的发生。本研究中我们试图解决如下几个关键的科学问题：1）肝内CD24表达与急性肝损伤的关系；2）CD24在肝内的细胞学分布；3）CD24分子调节急性肝损伤的细胞学基础和相关分子机理。本研究有助于系统阐明CD24分子调控急性肝损伤的免疫学机制，加深病原体在宿主肝内炎症反应调节机制的理解，为肝病治疗寻找新的药物。

Immunological regulation of acute liver injury is one of the major topics of today's immunology and liver disease research areas. In recent studies, CD24, also known as the heat-stable antigen (HSA), is expressed as a glycosyl-phosphatidyl-inositol (GPI)-anchored molecule, however, what the kinds of immunological cells in liver can express CD24 and how the CD24 regulates the inflammation remain unresolved. More recently, we found administration of anti-CD24 antibody caused rapid death of wild-type (WT) mice-induced by pertussis toxin (PTX) within 12 hours, which is accompanied by increasing amounts of serum alanine transaminase (ALT), aspartate aminotransferase (AST) and liver hemorrhage, meanwhile, we detected a massive increase in the inflammtory cytokines tumor necrosis factor-alpha (TNF-a) after PTX and anti-CD24 antibody treatment. Furthermore,using CD24-/- mice，we also got similar results. To test whether the absence of T and B cells can affect these results, we repeated these experiments using Rag-/- mice, and found all of these indicative of liver damage keeping the similar results,this suggests that CD24 regulating the mouse model of PTX-induced acute liver injury may be mainly related to liver innate immune.On the basis of these discoveries, we hypothesize that CD24 may serve as an important negative regulator for acute liver injury, which expresses on the surface of one or several kinds of the innate immunological cells in the liver, inhibits immune response and inflammation, and protects the host against attack of foreign pathogens and its derivatives. Therefore, we will try to explore the following key scientific questions: 1) what is the role of CD24 in acute liver injury? 2) How dose CD24 distribute in liver? 3) what is the molecular mechanisms of CD24 regulating acute liver injury? Our proposed studies will not only contribute to clarify the immunological mechanisms of CD24 in the regulation of acute liver injury, but also deepen the understanding of pathogen or damage-induced inflammatory response in the liver of host, furthermore, and to uncover new drug targets for the clinical treatment on liver diseases.