IL-4 and IL13 promote liver fibrosis signaling through M2 macrophages, but not Th2 T cells or hepatocytes

Weng, Shawn; Wang, X.; Vijayan, Santosh; Kim, Y.O.; Kaps, L.; Tang, Yi; Molokanova, O.; Crosby, Jeff; McCaleb, Michael L.; Brombacher, Frank; Waisman, Ari; Bockamp, Ernesto; Schuppan, Detlef

doi:10.1016/s0168-8278(17)31775-0

Cited by 5 publications

(6 citation statements)

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“…To further investigate the role of cytokines in fibrogenesis, conjoint analysis indicated that Th1/Th2 cytokines (IFN-γ/IL-4) were inclined to Th2 immune responses from 14-dpi to 28-dpi, which was consistent with the progress of fibrosis ( Supplementary Figure 1 , Supplementary Figure 6 ). These results indicated that the IL-4 might be the predominantly profibrogenic cytokines, which is consistent with CCl 4 -induced fibrosis in mice [ 12 ]. Those characteristics of liver injury, fibrosis and regeneration should be recognized as chronic viral hepatitis.…”

Section: Discussionsupporting

confidence: 65%

“…Briefly, CVH is transformed from Acute Viral Hepatitis (AVH) and is related to inflammatory responses, parenchymal cell necrosis or apoptosis and regeneration. Many human and animal model studies have revealed a correlation between inflammatory responses and fibrosis, which is caused by proliferation of hepatic stellate cells (HSCs) [ 11 , 12 ]. Additionally, approximately 5%-10% of adult patients with CVH may progress to liver cirrhosis [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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The neglected avian hepatotropic virus induces acute and chronic hepatitis in ducks: an alternative model for hepatology

Mao

Cao

et al. 2017

Oncotarget

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Duck Hepatitis A Virus (DHAV) belongs to the Avihepatovirus, which is also classified into Picornaviridae with Hepatovirus, Hepatitis A Virus (HAV). In humans, the pathogenesis of HAV is not well understood because of limited work with animal models. Here, we investigated the progress of duck viral hepatitis caused by DHAV and their potential for dissecting the pathogenesis of HAV. During the course of infection, the duck model had undergone hepatocellular lesions (vacuolation, acidophilic degeneration and steatosis), lymphocytes recruitment (neutrophil granulocytes, heterophilic granulocytes and T cells or plasm cells) and repair (activation of hepatic stellate cells, fibrosis and regeneration). Coincident with liver injury, the serum biomarkers, aspartate aminotransferase and alanine transaminase were significantly increased. Moreover, comparatively lower CD4+ and CD8+ T-cells were recruited to the liver, which might lead to a persistent infection (40 wk). Because DHAV and HAV have similar genomic structure, biological phenotypes and can easily replicate in liver. And half of fibrosis-related genes had high homology between humans and ducks. Considering these similarity in pathological and virological phenotypes, we proposed that the ducks might be an alternatively small animal model that would provide insight into the pathogenesis of viral hepatitis, fibrosis and liver regeneration.

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Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

The neglected avian hepatotropic virus induces acute and chronic hepatitis in ducks: an alternative model for hepatology

Mao

Cao

et al. 2017

Oncotarget

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“…IL-4 is necessary for the differentiation of Th2 cells (Fort et al, 2001;Kopf et al, 1993), It is multi-functions and can be secreted by different cells (Taylorfishwick, Kahan, Hiestand, Ritter, & Foxwell, 1993). Inf allergic diseases, ILC2s-derived IL-4 switches immunoglobulin class into IgE in B cells (Motomura et al, 2014), also in other inflammatory diseases, IL-4 can promote the transformation of macrophages into inflammatory M2 macrophages (Vannella et al, 2014;Weng et al, 2017). Moreover, IL-4 also plays a crucial role in tumor diseases.…”

Section: Il-4 In Tumor Immunitymentioning

confidence: 99%

Role of type 2 innate lymphoid cell and its related cytokines in tumor immunity

Wan

Cai

Wang

et al. 2019

Journal Cellular Physiology

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Type 2 innate lymphoid cells (ILC2s) have multiple functions that can respond to allergic diseases, parasite infection, metabolic homeostasis, tissue repair, and adipose metabolism homeostasis. In these diseases, ILC2s can be activated by various inflammatory cytokines released by damaged cells. Activated ILC2s produce different type 2 cytokines, including interleukin (IL)-4, IL-5, IL-9, and IL-13, which involved in the pathogenesis of many diseases. In recent years, the relationship between ILC2s and tumor diseases has attracted more and more attention. The role of ILC2s in tumor immunity depends on its surface molecules and cytokine context. This review aims to conclude tumorigenic and antitumorigenic roles of ILC2s, and the characters of ILC2s-related cytokines in tumor diseases to provide a comprehensive overview of the impact of ILC2s in tumor immunity.

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“…Therefore, regulating the role of macrophages is one of the new methods to treat liver fibrosis. [ 6 ]…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, regulating the role of macrophages is one of the new methods to treat liver fibrosis. [6] The tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) gene, which is located on chromosome 17p13.1, is a transmembrane protein consisting of 249 amino acids, and it can be classified as soluble and transmembrane types. [7] The soluble TWEAK (sTWEAK) can exert its regulatory role in numerous diseases through circulation.…”

mentioning

confidence: 99%

TWEAK promotes inflammatory response in liver fibrosis

Kong,

Yang,

et al. 2023

J Biochem & Molecular Tox

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This study aimed to investigate the role and mechanism of tumor necrosis factor‐like weak inducer of apoptosis (TWEAK) in liver fibrosis. The liver Kupffer cells (KCs) and mononuclear macrophages (J774A.1) were used as the objects of study to induce M1 polarization with LPS/IFN‐γ. After TWEAK intervention, the M1 cell proportion and marker cytokine levels were detected. Thereafter, CD266 expression was silenced, and NLRP3 expression was inhibited by the NLRP3 inhibitor, so as to investigate the impact of TWEAK on M1 polarization of KCs. In addition, the mouse model of liver fibrosis was constructed to observe the influence of TWEAK on mouse liver fibrosis. According to our results, TWEAK promoted M1 polarization of liver KCs and J774A.1 cells, and silencing CD266 expression or treatment with the NLRP3 inhibitor suppressed the effect of TWEAK. In the mouse experiment, it was discovered that after knocking down NLRP3 expression or using NLRP3 inhibitor to antagonize the effect of TWEAK, the mouse liver function and M1 cell level in liver tissues were improved.

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IL-4 and IL13 promote liver fibrosis signaling through M2 macrophages, but not Th2 T cells or hepatocytes

Cited by 5 publications

References 0 publications

The neglected avian hepatotropic virus induces acute and chronic hepatitis in ducks: an alternative model for hepatology

The neglected avian hepatotropic virus induces acute and chronic hepatitis in ducks: an alternative model for hepatology

Role of type 2 innate lymphoid cell and its related cytokines in tumor immunity

TWEAK promotes inflammatory response in liver fibrosis

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