Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice.
Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice.
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Interleukin-21 的上调通过驱动 GC 免疫反应和激活小鼠 HSC 促进血吸虫病的肝脏病理学
DOI：
10.1038/s41598-017-16783-7
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发表时间：
2017-11-30
影响因子：
4.6
通讯作者：
Xia C
中科院分区：
文献类型：
--
作者：
Wang Y;Lin C;Cao Y;Duan Z;Guan Z;Xu J;Zhu XQ;Xia C
血吸虫卵引起的肝脏肉芽肿、纤维化以及最终的肝脏疤痕的病理学是复杂的。 CD4+辅助性 T (Th) 细胞在针对寄生虫感染的宿主体液免疫和细胞免疫以及血吸虫病的免疫病理学中发挥着关键作用。滤泡辅助 T (Tfh) 细胞是 Th 细胞的另一个特殊亚群，与传染病有关。然而，Tfh细胞在血吸虫病严重肝脏病理中的免疫调节机制仍知之甚少。本研究利用日本血吸虫感染的小鼠模型，研究了体内Tfh细胞的动态和效应，并通过流式细胞术证明Tfh表型分子ICOS、PD-1和功能因子IL-21与疾病发生呈正相关。同时，我们的结果还表明，通过B-T共培养实验，随着肝脏免疫病理学的进展，Tfh细胞在脾生发中心（GC）富集并促进B细胞产生IgM。更重要的是，我们的数据表明，IL-21通过体外免疫组织化学检测和阻断试验驱动GC反应和激活HSC，从而促进肝卵肉芽肿的形成和发展以及随后的纤维化。我们的研究结果有助于更好地了解血吸虫病的免疫发病机制，并对肝纤维化疾病的治疗干预具有重要意义。
The pathology of schistosome egg-induced liver granuloma, fibrosis and eventually liver scarring is complicated. CD4+helper T (Th) cells play critical roles in both host humoral immunity and cellular immunity against parasitic infection and immunopathology in schistosomiasis. Follicular helper T (Tfh) cells are another specialized subset of Th cells and involved in infectious diseases. However, the immune regulatory mechanism of Tfh cells in severe liver pathology of schistosomiasis is still poorly understood. In this study, using aS.japonicum-infected mouse model, we studied the dynamics and effects of Tfh cellsin vivoand demonstrated that Tfh phenotype molecules ICOS, PD-1 and functional factor IL-21 were positively correlated with disease development by flow cytometry. Meanwhile, our results also showed that Tfh cells enriched in splenic germinal center (GC) and promoted B cells producing IgM with the progress of hepatic immunopathology by B-T co-culture experiments. More importantly, our data indicated that IL-21 contributed to the formation and development of hepatic egg granuloma and subsequent fibrosis by driving GC responses and activating HSCs by immunohistochemical detection and blocking assayin vitro. Our findings contribute to the better understanding of the immunopathogenesis of schistosomiasis and have implications for therapeutic intervention of hepatic fibrotic diseases.
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影响因子：
32.4
作者：
Choi YS;Kageyama R;Eto D;Escobar TC;Johnston RJ;Monticelli L;Lao C;Crotty S
通讯作者：
Crotty S
影响因子：
32.4
作者：
Nurieva, Roza I.;Chung, Yeonseok;Hwang, Daehee;Yang, Xuexian O.;Kang, Hong Soon;Ma, Li;Wang, Yi-Hong;Watowich, Stephanie S.;Jetten, Anton M.;Tian, Qiang;Dong, Chen
通讯作者：
Dong, Chen
影响因子：
56.9
作者：
Garside, P;Ingulli, E;Jenkins, MK
通讯作者：
Jenkins, MK
影响因子：
20.3
作者：
Eddahri, Fouad;Denanglaire, Sebastien;Andris, Fabienne
通讯作者：
Andris, Fabienne
影响因子：
32.4
作者：
Cucak, Helena;Yrlid, Ulf;Johansson-Lindbom, Bengt
通讯作者：
Johansson-Lindbom, Bengt