Interleukin-9 blockage reduces early hepatic granuloma formation and fibrosis during Schistosoma japonicum infection in mice

白细胞介素 9 阻断可减少小鼠日本血吸虫感染期间早期肝肉芽肿形成和纤维化

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作者:Tingzheng Zhan, Huihui Ma, Suqin Jiang, Zirong Zhong, Xiaoli Wang, Chunxiang Li, Dan Yu, Lei Liu, Jing Xu, Chaoming Xia

Abstract

Hepatic fibrosis induced by schistosomes is regulated by a complex network of cytokines. T helper type 9 (Th9) cells are a new type of effector T helper cells, which mainly secrete the specific cytokine interleukin-9 (IL-9). Interleukin-9 has been shown to contribute to liver fibrosis in patients with chronic hepatitis B and in a mouse model due to carbon tetrachloride. However, the role of IL-9 in schistosomiasis fibrosis remains unknown. In this study, we investigated the roles of IL-9 in schistosomiasis through in vivo and in vitro studies. The in vivo studies found that neutralization of IL-9 reduced liver granulomatous inflammation and collagen deposition around parasite eggs. The in vitro studies found that the treatment of primary hepatic stellate cells with IL-9 induced a significant increase of collagen and α-smooth-muscle actin. Moreover, we also described the dynamics and relevance of IL-9 and IL-4 in mice infected with Schistosoma japonicum. We found that IL-9 might appear more quickly and at higher levels than IL-4. Hence, our findings indicated that IL-9 might play a role in regulating hepatic fibrosis in early-stage schistosomiasis and become a promising approach for regulating hepatic fibrosis caused by S. japonicum.

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