Chronic inflammation involves CCL11 and IL-13 to facilitate the development of liver cirrhosis and fibrosis in chronic hepatitis B virus infection

Wong, Sui‐Weng; Ting, Yi-Wen; Yong, Yean-Kong; Tan, Hong-Yien; Barathan, Muttiah; Riazalhosseini, Behnaz; Bee, Chook Jack; Tee, Kok Keng; Larsson, Marie; Velu, Vijayakumar; Shankar, Esaki M.; Mohamed, Rosmawati

doi:10.1080/00365513.2021.1876245

Cited by 17 publications

(17 citation statements)

References 84 publications

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“… 34 However, we are first to show increased CCL11 expression in Sharpin-/- exposed mice. It has been suggested that IL-13 and CCL11 are involved in chronic liver inflammation in chronic hepatitis B viral infection 53 and IL4/IL13, which with TGF-β, has been shown importance in airway fibrosis in asthma. 54 Whether IL-4/IL-13 and CCL11 were synergistically involved in inducing chronic inflammation and tissue remodeling in esophagus in our model of EoE require further investigation.…”

Section: Discussionmentioning

confidence: 99%

Induction of Severe Eosinophilic Esophagitis and Multi-Organ Inflammation by Airborne Allergens is Associated with IL-4/IL-13 and CCL11 but Not IgE in Genetic Susceptible Mice

Maskey¹,

Soffer²,

Dunkin³

et al. 2022

JIR

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Background Eosinophilic Esophagitis (EoE) is an increasingly common chronic inflammatory disease. The pathological mechanisms underlying EoE are largely unknown. Objective We sought to understand the mechanisms underlying aeroallergen-induced EoE in Sharpin gene deficient (Sharpin-/-) mice that is prone to inflammatory response. Methods Sharpin-/-mice were exposed with Aspergillus fumigatus and ovalbumin intranasally every alternate day for 4 weeks. Wild type (WT) naïve mice, WT exposed, and un-exposed Sharpin-/- mice were controls. Histopathological analysis was performed by H&E, trichrome and major basic protein staining. Total and specific IgE, IgG, and IgA levels were measured by ELISA and Th2 cytokine and CCL11 chemokine gene expression were determined. Results Airborne allergen exposed Sharpin-/- mice showed severe eosinophilic inflammation in the esophagus (p < 0.001), and markedly increased epithelial thickening (p < 0.0001) compared to WT normal controls, whereas airborne allergen exposed WT mice and unexposed Sharpin-/- mice only showed mild eosinophilic inflammation in the esophagus. These exposed Sharpin-/- mice also showed over 7-fold increase in blood eosinophils (p < 0.0001), 60-fold increase in eosinophils in bronchoalveolar lavage fluid (p < 0.0001) and 4-fold increase in eosinophils in the skin (p < 0.0001) compared to normal controls. Surprisingly, exposed Sharpin-/- mice did not show elevation of serum total or antigen-specific IgE levels but reduced total IgA and IgG levels than normal controls There was a marked increase in IL-4, IL-13 and CCL11 gene expression in esophageal tissue (p < 0.001) in exposed Sharpin-/- mice compared to WT normal mice. Conclusion Th2 cytokines and chemokines, but not IgE may play an important pathologic role in aeroallergen-induced EoE. This study may provide insight into new therapeutics for EoE.

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Section: Discussionmentioning

confidence: 99%

Induction of Severe Eosinophilic Esophagitis and Multi-Organ Inflammation by Airborne Allergens is Associated with IL-4/IL-13 and CCL11 but Not IgE in Genetic Susceptible Mice

Maskey¹,

Soffer²,

Dunkin³

et al. 2022

JIR

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“…HBV viral load has not been associated with controlled attenuation parameter (CAP) liver stiffness measurement (LSM) scores in chronic HBV patients. The implication of metabolic components in liver disease progression and NAFLD development has also been shown in CHB patients, as they had a significant positive correlation with fibrosis/cirrhosis and hepatic steatosis ( 53 ). Specific plasma markers of CHB, such as CCL11, IL-6, IL-4, IL-13 and G-CSF have been shown to have a significant influence on the CAP and LSM scores independent of metabolic components.…”

Section: Effect Of Hbv Viral Load and Specific Plasma Markers On Nafl...mentioning

confidence: 91%

NAFLD and HBV interplay - related mechanisms underlying liver disease progression

Tourkochristou

Assimakopoulos²,

Thomopoulos³

et al. 2022

Front. Immunol.

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Non-alcoholic fatty liver disease (NAFLD) and Hepatitis B virus infection (HBV) constitute common chronic liver diseases with worldwide distribution. NAFLD burden is expected to grow in the coming decade, especially in western countries, considering the increased incidence of diabetes and obesity. Despite the organized HBV vaccinations and use of anti-viral therapies globally, HBV infection remains endemic and challenging public health issue. As both NAFLD and HBV have been associated with the development of progressive fibrosis, cirrhosis and hepatocellular carcinoma (HCC), the co-occurrence of both diseases has gained great research and clinical interest. The causative relationship between NAFLD and HBV infection has not been elucidated so far. Dysregulated fatty acid metabolism and lipotoxicity in NAFLD disease seems to initiate activation of signaling pathways that enhance pro-inflammatory responses and disrupt hepatocyte cell homeostasis, promoting progression of NAFLD disease to NASH, fibrosis and HCC and can affect HBV replication and immune encountering of HBV virus, which may further have impact on liver disease progression. Chronic HBV infection is suggested to have an influence on metabolic changes, which could lead to NAFLD development and the HBV-induced inflammatory responses and molecular pathways may constitute an aggravating factor in hepatic steatosis development. The observed altered immune homeostasis in both HBV infection and NAFLD could be associated with progression to HCC development. Elucidation of the possible mechanisms beyond HBV chronic infection and NAFLD diseases, which could lead to advanced liver disease or increase the risk for severe complications, in the case of HBV-NAFLD co-existence is of high clinical significance in the context of designing effective therapeutic targets.

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“…Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome where symptoms can range from accumulation of fatty droplets in liver cells to development of inflammatory steatohepatitis (NASH) that may further progress to liver fibrosis, cirrhosis and liver failure or onset of hepatocellular carcinoma (HCC). 77,78 Together with HBV, NAFLD represents the two most prevalent liver diseases reported from across the world. 77,79,80 Viral hepatitis and metabolic syndrome (e.g.…”

Section: Mait Cells and Non-alcoholic Fatty Liver Disease (Nafld)mentioning

confidence: 99%

“…77,78 Together with HBV, NAFLD represents the two most prevalent liver diseases reported from across the world. 77,79,80 Viral hepatitis and metabolic syndrome (e.g. obesity, type 2 diabetes (T2D), and hypertriglyceridemia) are the common precursors for the development of NAFLD and is usually reversible.…”

Section: Mait Cells and Non-alcoholic Fatty Liver Disease (Nafld)mentioning

confidence: 99%

“…Using a multivariate regression model, we found that plasma level of CCL11 was independently correlated with the LSM, where every increase of CCL11 by 10 ng/ml was associated with increase of relative risk of liver fibrosis by 0.26. 77 Since CCL11 (also known as eotaxin) is an eosinophil recruiting chemokine, and level of CCL11 is inducible by IL-17A, 101 infiltration of eosinophils into the liver can observed in many liver diseases including HCV infection, 102 drug induced hepatitis 103 and NAFLD. 104,105 Given that eosinophil is a transforming growth factor-β (TGF-β) producer and TGF-β itself is a profibrotic cytokine, perpetuating elevation of TGF-β can cause liver fibrosis.…”

Section: Mait Cells and Non-alcoholic Fatty Liver Disease (Nafld)mentioning

confidence: 99%

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Mucosal-Associated Invariant T Cells: Diplomatic Front-Runners in the Fight against Hepatitis B Virus Infection

Yien

Kong

et al. 2021

Crit Rev Immunol

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Mucosal-associated invariant T (MAIT) cells are a unique subset of innate-like T cells that bridge between innate and adaptive immunity. MAIT cells act like a 'biliary firewall' protecting the epithelial lining of the liver against pathogenic intruders. MAIT1 and MAIT17 subsets respond rapidly to pathogenic presence both in the liver as well as in the peripheral circulation. Besides chronic HBV infection, MAIT cells also appear to serve as potential therapeutic targets in several other chronic ailments. Evidence indicates that MAIT cells have tissue repair functions also paving way for fibrotic changes during chronic HBV infection. Observations also suggest that HBV-HDV co-infection disease progression is closely associated with loss of MAIT cells. Furthermore, reduction in the number of hepatic MAIT cells in patients with cirrhotic NAFLD and HBV-associated primary liver cancer has also been reported. Given their concrete role against HBV disease progression, and has also become evident that the tumor microenvironment can cause functional impairment of MAIT cells. Here, we reviewed the protective and the pathological role of MAIT cells in chronic HBV infection and certain other related medical conditions based on the understanding that an optimal functioning of the MAIT cell arsenal is key to a 'host-friendly' immune defense against HBV disease progression.

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Chronic inflammation involves CCL11 and IL-13 to facilitate the development of liver cirrhosis and fibrosis in chronic hepatitis B virus infection

Cited by 17 publications

References 84 publications

Induction of Severe Eosinophilic Esophagitis and Multi-Organ Inflammation by Airborne Allergens is Associated with IL-4/IL-13 and CCL11 but Not IgE in Genetic Susceptible Mice

Induction of Severe Eosinophilic Esophagitis and Multi-Organ Inflammation by Airborne Allergens is Associated with IL-4/IL-13 and CCL11 but Not IgE in Genetic Susceptible Mice

NAFLD and HBV interplay - related mechanisms underlying liver disease progression

Mucosal-Associated Invariant T Cells: Diplomatic Front-Runners in the Fight against Hepatitis B Virus Infection

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