Hepatocyte CD1d protects against liver immunopathology in mice with schistosomiasis japonica
Hepatocyte CD1d protects against liver immunopathology in mice with schistosomiasis japonica
复制标题
肝细胞 CD1d 可预防日本血吸虫病小鼠的肝脏免疫病理学变化
DOI：
10.1111/imm.13288
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发表时间：
2020-12-22
期刊：
影响因子：
6.4
通讯作者：
Su, Chuan
中科院分区：
文献类型：
--
作者：
Lei, Zhigang;Tang, Rui;Su, Chuan
血吸虫病是一种被忽视的热带疾病，全世界有2.5亿多人感染。曼氏血吸虫（Schistosoma mansoni，S. mansoni）和日本血吸虫（S.日本血吸虫）引起针对组织捕获的虫卵的炎症反应，导致主要在宿主肝脏中形成肉芽肿。持续性肉芽肿反应导致肝脏严重纤维化，导致肝脏不可逆损伤，甚至宿主死亡。CD 1d是一种高度保守的MHC I类分子，由造血细胞和非造血细胞表达。造血来源的抗原呈递细胞（APC）上的CD 1d将病原体衍生的脂质抗原呈递给自然杀伤T（NKT）细胞，这使得它们能够快速产生大量的各种细胞因子，并在病原体入侵时促进CD 4（+）T辅助（Th）细胞分化。值得注意的是，非造血来源的肝细胞最近已被证明通过CD 1d依赖性方式参与维持肝脏NKT细胞稳态。然而，肝细胞CD 1d依赖性调节NKT细胞稳态是否也调节CD 4（+）Th细胞反应和小鼠血吸虫病肝脏免疫病理学仍有待解决。在这里，我们发现小鼠肝细胞上的CD 1d表达在S.日本血吸虫感染，伴随着增加的NKT细胞，以及上调Th 1和Th 2反应。CD 1d在肝细胞中的过表达显著降低了局部NKT数量和细胞因子（IFN-γ、IL-4、IL-13），同时下调了Th 1和Th 2应答，减轻了肝组织的病理损伤。日本血吸虫感染小鼠。这些发现突出了肝细胞CD 1d靶向治疗在血吸虫病肝脏免疫病理学控制中的潜力。
Schistosomiasis is a neglected tropical disease with over 250 million people infected worldwide. The main clinically important species Schistosoma mansoni (S. mansoni) and Schistosoma japonicum (S. japonicum) cause inflammatory responses against tissue-trapped eggs, resulting in formation of granulomas mainly in host liver. Persistent granulomatous response results in severe fibrosis in the liver, leading to irreversible impairment of the liver and even death of the host. CD1d, a highly conserved MHC class I-like molecule, is expressed by both haematopoietic and non-haematopoietic cells. CD1d on antigen-presenting cells (APCs) of haematopoietic origin presents pathogen-derived lipid antigens to natural killer T (NKT) cells, which enables them to rapidly produce large amounts of various cytokines and facilitate CD4(+) T helper (Th) cell differentiation upon invading pathogens. Noteworthy, hepatocytes of non-haematopoietic origin have recently been shown to be involved in maintaining liver NKT cell homeostasis through a CD1d-dependent manner. However, whether hepatocyte CD1d-dependent regulation of NKT cell homeostasis also modulates CD4(+) Th cell responses and liver immunopathology in murine schistosomiasis remains to be addressed. Here, we show in mice that CD1d expression on hepatocytes was decreased dramatically upon S. japonicum infection, accompanied by increased NKT cells, as well as upregulated Th1 and Th2 responses. Overexpression of CD1d in hepatocytes significantly decreased local NKT numbers and cytokines (IFN-gamma, IL-4, IL-13), concomitantly with downregulation of both Th1 and Th2 responses and alleviation in pathological damage in livers of S. japonicum-infected mice. These findings highlight the potential of hepatocyte CD1d-targeted therapies for liver immunopathology control in schistosomiasis.