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Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice

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...

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Autores principales: Wang, Yanyan, Lin, Cai, Cao, Yun, Duan, Zhongliang, Guan, Zhixun, Xu, Jing, Zhu, Xing-Quan, Xia, Chaoming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709429/
https://www.ncbi.nlm.nih.gov/pubmed/29192177
http://dx.doi.org/10.1038/s41598-017-16783-7
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author Wang, Yanyan
Lin, Cai
Cao, Yun
Duan, Zhongliang
Guan, Zhixun
Xu, Jing
Zhu, Xing-Quan
Xia, Chaoming
author_facet Wang, Yanyan
Lin, Cai
Cao, Yun
Duan, Zhongliang
Guan, Zhixun
Xu, Jing
Zhu, Xing-Quan
Xia, Chaoming
author_sort Wang, Yanyan
collection PubMed
description 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 a S. japonicum-infected mouse model, we studied the dynamics and effects of Tfh cells in vivo and 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 assay in 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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spelling pubmed-57094292017-12-06 Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice Wang, Yanyan Lin, Cai Cao, Yun Duan, Zhongliang Guan, Zhixun Xu, Jing Zhu, Xing-Quan Xia, Chaoming Sci Rep Article 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 a S. japonicum-infected mouse model, we studied the dynamics and effects of Tfh cells in vivo and 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 assay in vitro. Our findings contribute to the better understanding of the immunopathogenesis of schistosomiasis and have implications for therapeutic intervention of hepatic fibrotic diseases. Nature Publishing Group UK 2017-11-30 /pmc/articles/PMC5709429/ /pubmed/29192177 http://dx.doi.org/10.1038/s41598-017-16783-7 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Yanyan
Lin, Cai
Cao, Yun
Duan, Zhongliang
Guan, Zhixun
Xu, Jing
Zhu, Xing-Quan
Xia, Chaoming
Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice
title Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice
title_full Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice
title_fullStr Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice
title_full_unstemmed Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice
title_short Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice
title_sort up-regulation of interleukin-21 contributes to liver pathology of schistosomiasis by driving gc immune responses and activating hscs in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709429/
https://www.ncbi.nlm.nih.gov/pubmed/29192177
http://dx.doi.org/10.1038/s41598-017-16783-7
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