Role of interleukin-23 in monocyte-derived dendritic cells of HBV-related acute-on-chronic liver failure and its correlation with the severity of liver damage

Bao, Suxia; Zheng, Jianming; Li, Ning; Huang, Chong; Chen, Mingquan; Cheng, Qi; Li, Qian; Lü, Qing; Zhu, Mengqi; Ling, Qingxia; Yu, Kangkang; Chen, Shengshen; Shi, Guangfeng

doi:10.1016/j.clinre.2016.10.005

Cited by 24 publications

(22 citation statements)

References 25 publications

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“…In terms of HBV, IL-4 gene polymorphisms may affect the Korean infants’ response to the HBV vaccine [24]. And the level of IL-23 in monocyte-derived dendritic cells was associated with mortality of acute-on-chronic liver failure (HBV-ACLF) patients [25]. So far, there is no report about the relationship between HBV and IL-34.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-34 inhibits hepatitis B virus replication in vitro and in vivo

et al. 2017

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BackgroundThe hepatitis B virus (HBV) infection could activate the immune system and induce extensive inflammatory response. As the most important inflammatory factor, interleukins are critical for anti-viral immunity. Here we investigated whether interleukin-34 (IL-34) play a role in HBV infection.Methodology/Principal findingsIn this study, we first found that both serum IL-34 and IL-34 mRNA in PBMCs in chronic HBV patients was significantly decreased compared to the healthy controls. Furthermore, both IL-34 protein and mRNA levels were declined hepatoma cells expressing HBV. In addition, the clinical parameters analysis found that serum IL-34 was significantly associated with HBV DNA (P = 0.0066), ALT (P = 0.0327), AST (P = 0.0435), TB (P = 0.0406), DB (P = 0.0368) and AFP (P = 0.0225). Correlation analysis also found that serum IL-34 negatively correlated with HBV DNA copies, ALT and AST. In vitro studies found that IL-34 treatment in HepAD38 and HepG2.2.15 cells markedly inhibited HBV DNA, total RNA, 3.5kb mRNA and HBc protein. In vivo studies further demonstrated IL-34 treatment in HBV transgenic mice exhibited greater inhibition on HBV DNA, total RNA, 3.5kb mRNA and HBc protein, suggesting the effect to IL-34 on HBV is likely due to host innate or adaptive immune response.Conclusions/SignificanceOur study identified a novel interleukin, IL-34, which has anti-viral activity in HBV replication in hepatocytes in vitro and in vivo. These data suggest a rationale for the use of IL-34 in the HBV treatment.

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Section: Discussionmentioning

confidence: 99%

Interleukin-34 inhibits hepatitis B virus replication in vitro and in vivo

et al. 2017

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“…In ACLF, monocytes derived dendritic cells (MoDCs) produce high amount of IL-23 and express its cognate receptor IL-23R. Higher IL-23 production in non-survivors are associated with MELD, INR, prothrombin time, and total bilirubin level and signify potential contribution in disease progression and severity (101). MoDCs showed upraised NF-κB and TNF receptor associated factor-6 (TRAF6) expression which was related to the elevated level of IL-23.…”

Section: Dcsmentioning

confidence: 99%

Abnormal Innate Immunity in Acute-on-Chronic Liver Failure: Immunotargets for Therapeutics

Khanam

Kottilil

2020

Front. Immunol.

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Acute-on-chronic liver failure (ACLF) is a severe life-threatening condition with high risk of multiorgan failure, sepsis, and mortality. ACLF activates a multifaceted interplay of both innate and adaptive immune response in the host which governs the overall outcome. Innate immune cells recognize the conserved elements of microbial and viral origin, both to extort instant defense by transforming into diverse modules of effector responses and to generate long-lasting immunity but can also trigger a massive intrahepatic immune inflammatory response. Acute insult results in the activation of innate immune cells which provokes cytokine and chemokine cascade and subsequently initiates aggressive systemic inflammatory response syndrome, hepatic damage, and high mortality in ACLF. Dysregulated innate immune response not only plays a critical role in disease progression but also potentially correlates with clinical disease severity indices including Child-Turcotte-Pugh, a model for end-stage liver disease, and sequential organ failure assessment score. A better understanding of the pathophysiological basis of the disease and precise immune mechanisms associated with liver injury offers a novel approach for the development of new and efficient therapies to treat this severely ill entity. Immunotherapies could be helpful in targeting immune-mediated organ damage which may constrain progression toward liver failure and eventually reduce the requirement for liver transplantation. Here, in this review we discuss the defects of different innate immune cells in ACLF which updates the current knowledge of innate immune response and provide potential targets for new therapeutic interventions.

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“…IL‐23R plays a pivotal role in the generation and differentiation of pathogenic Th17 cells. IL‐23R mediated signalling requires the binding of its cognate cytokine IL‐23, secreted by macrophages and dendritic cells . IL‐23R leads to activation of STAT3 pathway resulting in functional activation and maturation of Th17 cells .…”

Section: Introductionmentioning

confidence: 99%

“…Also, HBV infection induces IL‐23 production by antigen presenting cells and leads to liver damage via the IL‐23/IL‐17 axis . Importantly, elevated level of IL‐23 cytokine has been observed in serum as well as in monocyte‐derived dendritic cells of HBV‐related ACLF patients which is associated with high mortality . However, role of IL‐23 receptor and its involvement in severity of ACLF patients remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Increased interleukin‐23 receptor (IL‐23R) expression is associated with disease severity in acute‐on‐chronic liver failure

Khanam

Trehanpati

Sarin

2019

Liver International

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Abbreviations: ACLF, acute-on-chronic liver failure; CCR6, chemokine receptor 6; CHB, chronic hepatitis B; CTP, Child-Turcotte-Pugh; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-17R, interleukin-17 receptor; IL-23R, interleukin-23 receptor; IL-, interleukin; INR, international normalized ratio; MELD, Model for End-Stage Liver Disease; ROR-γt, retinoic acid receptor-related orphan nuclear receptor gamma t. AbstractBackground: Th17 cells mediated immune response is important in chronic hepatitis B (CHB) infection and inflammation associated diseases; however, little is known about their immunopathogenic role in acute-on-chronic liver failure (ACLF).Interleukin-23 receptor (IL-23R) is essential for the generation of pathogenic Th17 cells; therefore, we aimed to evaluate IL-23R expression and its correlation with disease severity in ACLF. Methods:Forty-two patients with ACLF (HBV and alcohol-related), thirty-two with CHB and twenty healthy controls (HC) were studied. Circulating and intrahepatic profile of Th17 cells and IL-23R was investigated. Association of IL-23R with disease severity was determined.Results: Circulating Th17 cells were significantly increased in both ACLF groups (P = 0.03, P = 0.006) than CHB and HC. Percentage of Th17 cells was higher in liver than peripheral blood of ACLF patients (P = 0.04). Expression of IL-23R was immensely up-regulated on Th17 cells of ACLF patients. Importantly, IL-23R not only correlated with the increased percentage of Th17 cells but also had significant association with inflammation (P = 0.03) and clinical disease severity indices including Child-Turcotte-Pugh (P = 0.001) and Model for End-Stage Liver Disease (P = 0.002) scores. The ACLF non-survivors showed higher IL-23R expression (P = 0.01).Transcription factor retinoic acid receptor-related orphan nuclear receptor gamma-t (ROR-γt) was also high in circulation and in liver of ACLF patients and it positively correlated with ALT levels (P = 0.03). Surface receptors, including CCR6, IL-17R and pro-inflammatory cytokines IL-17A, IL-22, CXCL8 and GM-CSF were highly augmented in ACLF. Conclusion: ACLF patients express high IL-23R on Th17 cells which induces inflam-mation and strongly correlates with liver disease severity. K E Y W O R D S alcoholic hepatitis, cirrhosis, hepatitis B, IL-17A, IL-23R, liver failure | 1063 KHANAM et Al.

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Role of interleukin-23 in monocyte-derived dendritic cells of HBV-related acute-on-chronic liver failure and its correlation with the severity of liver damage

Cited by 24 publications

References 25 publications

Interleukin-34 inhibits hepatitis B virus replication in vitro and in vivo

Interleukin-34 inhibits hepatitis B virus replication in vitro and in vivo

Abnormal Innate Immunity in Acute-on-Chronic Liver Failure: Immunotargets for Therapeutics

Increased interleukin‐23 receptor (IL‐23R) expression is associated with disease severity in acute‐on‐chronic liver failure

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