IL-33通过促进ST2+Treg细胞增殖减轻血吸虫感染宿主肝脏虫卵肉芽肿及纤维化免疫病理损害的机制研究

日本血吸虫感染后，沉积于肝脏的虫卵引起的肝脏肉芽肿是日本血吸虫感染主要的病理反应，过度（持续、快速）的虫卵肉芽肿反应可触发严重的肝纤维化，甚至危及宿主的生命。因此，日本血吸虫感染后对肝脏虫卵肉芽肿及纤维化进行适度有效的控制极为重要。Treg细胞可以抑制其他类型免疫细胞活性及分泌功能，在日本血吸虫感染过程中发挥着抑制虫卵肉芽肿的作用。但是日本血吸虫感染过程中肝脏Treg细胞数量调控的详细机制仍不清楚。我们前期研究中发现肝脏Treg细胞高表达IL-33受体。小鼠感染日本血吸虫后诱导的IL-33可激活ST2进而促进Treg细胞在肝脏中迅速增多。结合前期研究和文献报道，我们推测这一过程可能依赖于PI3K-Akt-GSK3β信号通路并拟开展实验证明。本研究为清楚了解日本血吸虫感染后虫卵肉芽肿及纤维化形成及调控提供了新的思路，同时也为其他类型的炎症性肝脏疾病的治疗提供新的靶点。

The liver granuloma is most important pathological damage caused by eggs deposited in the liver during schistosoma japonicum infection. Excessive (sustained, rapid) liver granuloma can promote the development of liver fibrosis in the later stage of infection and eventually endanger human health. Therefore, it is important to moderately and effectively control of liver granuloma and fibrosis after schistosoma infection. Treg cells are regulatory CD4+ T cells that inhibit the activity and secretion of other types of immune cells and play an important role in inhibiting the liver granuloma during schistosoma infection. Whereas, the detailed mechanism of tissue microenvironment regulates the proliferation of Treg cells after infection remains unclear. In pre-experiments, we found that, the liver Treg cells high expression of receptor for IL-33. After infection with schistosomiasis in mice, Treg cells were rapidly increased in the liver of mice.Combined with the previous work and references, we speculate that this process may depend on the PI3K-Akt-GSK3β signaling pathway. Our study not only provides a theoretical basis for the regulation of egg granuloma and liver fibrosis in schistosoma, but also provides a new target for the treatment for other types of inflammatory liver diseases.