Interleukin‐9 blockage reduces early hepatic granuloma formation and fibrosis during <i>Schistosoma japonicum</i> infection in mice

Zhan, Tianzuo; Ma, Hongfang; Jiang, Shengjie; Zhong, Zirong; Wang, Xiaoli; Li, Chunxiang; Yu, Di; Liu, Lei; Xu, Jing; Xia, Chao-Ming

doi:10.1111/imm.13111

Cited by 20 publications

(20 citation statements)

References 45 publications

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Section: Il-9 May Be Associated With Liver Fibrosismentioning

confidence: 84%

“…The expression of IL-9 is significantly higher in human liver cirrhosis tissue than that in the normal liver tissue [206] . CCl4 treatment of IL-9-overexpressing mice with recombinant adenovirus vector leads to severe liver fibrosis with increased collagen accumulation and α-smooth-muscle actin (α-SMA) expression levels [206] . Anti-IL-9 antibody treatment in mice treated with CCl4 (hepatic fibrosis mouse model) attenuates the development of hepatic inflammation, necrosis, and fibrosis, accompanied by a marked decrease in the number of activated HSCs [204] .…”

Section: Il-9 May Be Associated With Liver Fibrosismentioning

confidence: 84%

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Role of CD4+ T-cells in the pathology of non-alcoholic fatty liver disease and related diseases

Seike¹,

Mizukoshi²,

Kaneko³

2021

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Non-alcoholic fatty liver disease (NAFLD), which is considered a liver phenotype of metabolic diseases, is becoming a major cause of chronic liver disease. Multiple factors influence and interact with each other in a complex manner to form this pathological condition. As evidenced by low-grade chronic inflammation in obesity, which is a basic pathological feature of NAFLD, immune cell infiltration can occur in various organs, and immune cell infiltration into the liver plays an important role in the development of steatohepatitis. In recent years, an increasing number of reports indicate the involvement of innate immunity and adaptive immunity in the pathogenesis of NAFLD. CD4 + T-cells, which serve as an essential and complex element of the immune system and major regulators of host health and disease, are differentiated into functional T helper 1 (Th1), Th2, Th9, Th17, Th22, T follicular helper, and regulatory T-cells upon antigen stimulation in a special cytokine environment. In NAFLD patients, various pathological conditions such as obesity, diabetes, dyslipidemia, and adipose tissue inflammation coexist. Hence, T-cells can be affected by each of these pathological conditions. This review covers and discusses the reports on NAFLD and its associated pathologies as well as their effects on CD4 + T-cells.

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Section: Il-9 May Be Associated With Liver Fibrosismentioning

confidence: 84%

Section: Il-9 May Be Associated With Liver Fibrosismentioning

confidence: 84%

Role of CD4+ T-cells in the pathology of non-alcoholic fatty liver disease and related diseases

Seike¹,

Mizukoshi²,

Kaneko³

2021

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“…Consistently, intraperitoneal injection of anti-IL-9 antibody inhibits granulomatous inflammation in the liver and collagen deposition around the eggs of infected mice. Furthermore, direct stimulation of HSCs in vitro with IL-9 significantly increases the production of collagen and α-SMA ( 13 ). In addition, Th9 cells and IL-9 are increased in the blood of patients with HBV and HBV-related cirrhosis.…”

Section: Immune Cells and Related Cytokines In Pro-hepatic Fibrosismentioning

confidence: 99%

Novel Immune Subsets and Related Cytokines: Emerging Players in the Progression of Liver Fibrosis

et al. 2021

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Liver fibrosis is a pathological process caused by persistent chronic injury of the liver. Kupffer cells, natural killer (NK) cells, NKT cells, and dendritic cells (DCs), which are in close contact with T and B cells, serve to bridge innate and adaptive immunity in the liver. Meanwhile, an imbalanced inflammatory response constitutes a challenge in liver disease. The dichotomous roles of novel immune cells, including T helper 17 (Th17), regulatory T cells (Tregs), mucosa-associated invariant T cells (MAIT), and innate lymphoid cells (ILCs) in liver fibrosis have gradually been revealed. These cells not only induce damage during liver fibrosis but also promote tissue repair. Hence, immune cells have unique, and often opposing, roles during the various stages of fibrosis. Due to this heterogeneity, the treatment, or reversal of fibrosis through the target of immune cells have attracted much attention. Moreover, activation of hepatic stellate cells (HSCs) constitutes the core of fibrosis. This activation is regulated by various immune mediators, including Th17, Th22, and Th9, MAIT, ILCs, and γδ T cells, as well as their related cytokines. Thus, liver fibrosis results from the complex interaction of these immune mediators, thereby complicating the ability to elucidate the mechanisms of action elicited by each cell type. Future developments in biotechnology will certainly aid in this feat to inform the design of novel therapeutic targets. Therefore, the aim of this review was to summarize the role of specific immune cells in liver fibrosis, as well as biomarkers and treatment methods related to these cells.

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“…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 ]. Some factors, including IL-10, Tregs, B cells, antibodies, T cell anergy, macrophages, and microRNAs, are related to the pathogenic immune response in schistosomiasis [ 6 ].…”

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

Cited by 20 publications

References 45 publications

Role of CD4+ T-cells in the pathology of non-alcoholic fatty liver disease and related diseases

Role of CD4+ T-cells in the pathology of non-alcoholic fatty liver disease and related diseases

Novel Immune Subsets and Related Cytokines: Emerging Players in the Progression of Liver Fibrosis

Schistosoma japonicum Infection in Treg-Specific USP21 Knockout Mice

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