Schistosoma japonicum Infection Promotes the Response of Tfh Cells Through Down-Regulation of Caspase-3–Mediating Apoptosis

Yang, Quan; Qu, Jiale; Jin, Chenxi; Feng, Yuanfa; Xie, Shihao; Zhu, Jinxin; Liu, Gaoshen; Xie, Hongyan; Qiu, Huaina; Qi, Yanwei; Mu, Jianbing; Huang, Jun

doi:10.3389/fimmu.2019.02154

Cited by 13 publications

(14 citation statements)

References 42 publications

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“…Schistosomiasis is one of the most serious parasitic diseases worldwide and is also raised as a critical public health issue affecting nearly 200 million people in tropical and subtropical regions (1). The main pathological characteristic of schistosomiasis is the massive deposition of eggs in the liver and intestine, which causes the release of soluble antigen and finally leads to granuloma and subsequent liver fibrosis (2,3). Accordingly, liver fibrosis is an important risk factor for the development of ultimately cirrhosis, portal hypertension, and hepatocarcinoma (HCC), or even death (4).…”

Section: Introductionmentioning

confidence: 99%

MiR-130a-3p Alleviates Liver Fibrosis by Suppressing HSCs Activation and Skewing Macrophage to Ly6Clo Phenotype

Liu

Wang

et al. 2021

Front. Immunol.

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Emerging evidences have highlighted the crucial role of microRNAs (miRNAs) in the liver cirrhosis, but the relationship between miR-130a-3p and liver cirrhosis is not entirely clear. As we all know, schistosomiasis, as one of the zoonoses, can lead to liver cirrhosis when it advances. In this study, we investigated the biological functions of miR-130a-3p on the liver fibrosis of schistosomiasis in vivo and in vitro. The mice infected with Schistosoma japonicum (S. japonicum) were treated with lentivirus vector (LV)-miR-130a-3p by hydrodynamic injection through the tail vein. Our findings showed significantly decreased expression of miR-130a-3p both in the serum of patients with cirrhosis and in the liver of mice infected with S. japonicum. The results showed that LV-miR-130a-3p could effectively enter into the liver and alleviate liver granulomatous inflammation and collagen deposition. Simultaneously, LV-miR-130a-3p-promoted macrophages presented the Ly6Clo phenotype, concomitant with the decreased expression of the tissue inhibitor of metalloproteinases (TIMP) 1, and increased the expression of matrix metalloproteinase (MMP) 2, which contributed to the dissolution of collagen. Furthermore, overexpression of miR-130a-3p not only inhibited the activation and proliferation of hepatic stellate cells (HSCs) but also induced the apoptosis of HSCs. In addition, we also confirmed that miR-130a-3p enables to bind with mitogen-activated protein kinase (MAPK) 1 and transforming growth factor-beta receptors (TGFBR) 1 and TGFBR2 genes and inhibit the expressions of these genes. Our findings suggested that miR-130a-3p might represent as the potential candidate biomarker and therapeutic target for the prognosis identification and treatment of schistosomiasis liver fibrosis.

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Section: Introductionmentioning

confidence: 99%

MiR-130a-3p Alleviates Liver Fibrosis by Suppressing HSCs Activation and Skewing Macrophage to Ly6Clo Phenotype

Liu

Wang

et al. 2021

Front. Immunol.

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“…Parasites in the developmental stages express hundreds of antigenic moieties, many of which stimulate strong humoral and cellular immune responses [ 3 ]. Some of these responses continue to increase during chronic infection, and others are substantially reduced [ 4 ]. Observations in experimental mouse models of infection have elucidated the mechanisms governing the development and regulation of the pathogenic immune response in schistosomiasis [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Schistosoma japonicum Infection in Treg-Specific USP21 Knockout Mice

Zhang

Xiong

et al. 2021

Journal of Immunology Research

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The E3 deubiquitinating enzyme ubiquitin-specific proteolytic enzyme 21 (USP21) plays vital roles in physiological activities and is required for Treg-cell-mediated immune tolerance. Using a murine model infected with Schistosoma japonicum, we observed that there were more cercariae developed into adults and more eggs deposited in the livers of the USP21fl/flFOXP3Cre (KO) mice. However, immunohistochemistry showed that the degree of egg granuloma formation and liver fibrosis was reduced. In USP21fl/flFOXP3Cre mice, levels of IFN-gamma, IL-4, anti-soluble egg antigen (SEA) IgG and anti-soluble worm antigen preparation (SWAP) IgG increased in blood, as determined using ELISAs and multiplex fluorescent microsphere immunoassays, while the levels of IL-10, lL-17A, IL-23, IL-9, and anti-SEA IgM decreased. In addition, the levels of the USP21 protein and mRNA in the liver and spleen of KO mice decreased. We further observed increased Th1 responses amplified by Tregs (regulatory T cells) and compromised Th17 responses, which alleviated the liver immunopathology. We speculated that these changes were related to polarization of Th1-like Tregs. Our results revealed the roles of USP21 in Treg-cell-mediated regulation of immune interactions between Schistosoma and its host. USP21 may have potential for regulating hepatic fibrosis in patients with schistosomiasis.

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“…Once infected, the eggs released by S. japonicum is the major pathogenic substance, which can deposit on multiple organs (liver, etc.) in the body, causing damage, leading to liver fibrosis and splenomegalia ( 3 ). A variety of immune cells participate in the immune response caused by S. japonicum infection, and CD4 + T cells (Th cells) play an important role ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…It is known that ICOS participates in the proliferation and differentiation of CD4 + T cells. In studies involving infection with S. japonicum , the expression of ICOS was significantly increased ( 3 ). Similarly, in Trichinella spiralis infection model, blocking ICOS resulted in a decrease in the expressions of TNF-α and the Th2 cytokines (e.g., IL-4 and IL-5) and the serum levels of total IgE.…”

Section: Introductionmentioning

confidence: 99%

Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice

et al. 2021

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BackgroundTh cells (helper T cells) have multiple functions in Schistosoma japonicum (S. japonicum) infection. Inducible co-stimulator (ICOS) is induced and expressed in activated T lymphocytes, which enhances the development of B cells and antibody production through the ICOS/ICOSL pathway. It remains unclear about the role and possible regulating mechanism of ICOS+ Th cells in the spleen of S. japonicum-infected C57BL/6 mice.MethodsC57BL/6 mice were infected with cercariae of S. japonicum through the abdomen. The expression of ICOS, activation markers, and the cytokine production on CD4+ ICOS+ Th cells were detected by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR). Moreover, the differentially expressed gene data of ICOS+ and ICOS− Th cells from the spleen of infected mice were obtained by mRNA sequencing. Besides, Western blot and chromatin immunoprecipitation (ChIP) were used to explore the role of Ikzf2 on ICOS expression.ResultsAfter S. japonicum infection, the expression of ICOS molecules gradually increased in splenic lymphocytes, especially in Th cells (P < 0.01). Compared with ICOS− Th cells, more ICOS+ Th cells expressed CD69, CD25, CXCR5, and CD40L (P < 0.05), while less of them expressed CD62L (P < 0.05). Also, ICOS+ Th cells expressed more cytokines, such as IFN-γ, IL-4, IL-10, IL-2, and IL-21 (P < 0.05). RNA sequencing results showed that many transcription factors were increased significantly in ICOS+ Th cells, especially Ikzf2 (P < 0.05). And then, the expression of Ikzf2 was verified to be significantly increased and mainly located in the nuclear of ICOS+ Th cells. Finally, ChIP experiments and dual-luciferase reporter assay confirmed that Ikzf2 could directly bind to the ICOS promoter in Th cells.ConclusionIn this study, ICOS+ Th cells were found to play an important role in S. japonicum infection to induce immune response in the spleen of C57BL/6 mice. Additionally, Ikzf2 was found to be one important transcription factor that could regulate the expression of ICOS in the spleen of S. japonicum-infected C57BL/6 mice.

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Schistosoma japonicum Infection Promotes the Response of Tfh Cells Through Down-Regulation of Caspase-3–Mediating Apoptosis

Cited by 13 publications

References 42 publications

MiR-130a-3p Alleviates Liver Fibrosis by Suppressing HSCs Activation and Skewing Macrophage to Ly6Clo Phenotype

MiR-130a-3p Alleviates Liver Fibrosis by Suppressing HSCs Activation and Skewing Macrophage to Ly6Clo Phenotype

Schistosoma japonicum Infection in Treg-Specific USP21 Knockout Mice

Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice

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