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

Khanam, Arshi; Trehanpati, Nirupma; Sarin, Shiv Kumar

doi:10.1111/liv.14015

Cited by 20 publications

(15 citation statements)

References 42 publications

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“…Currently, the pathogenesis of CHB is not well elucidated. Accumulating evidence suggests that Th17 cells are critically involved in the pathogenesis of liver diseases, including CHB, 22 HBV‐related cirrhosis 5 and ACLF 23 . Our previous studies also confirmed that the proportion of Th17 cells is significantly increased in CHB, HBV‐ACLF 7 and HBV‐LF 8 .…”

Section: Discussionsupporting

confidence: 82%

HBV promotes the recruitment of IL‐17 secreting T cells via chemokines CCL22 and CCL17

Zhang

Liu

Yang

et al. 2020

Liver International

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Background and Aims:Little is known about the mechanisms of IL-17 secreting T cells accumulation in HBV-transfected livers. Here, we investigated the role of the chemokines CCL17, CCL20 and CCL22 in this process. Methods:Peripheral blood and liver tissues were obtained from 30 chronic hepatitis B (CHB) patients and 15 healthy volunteers and were evaluated by flow cytometric analysis and immunohistochemistry. Chemokine production by monocyte-derived dendritic cells (MoDCs) cocultured with HBV-transfected or untransfected Huh7 cells was measured by quantitative real-time PCR and enzyme-linked immunosorbent assay. The chemotactic activity of the culture supernatants was also tested. Results:The proportions of IL-17 secreting CD4 (Th17) and CD8 (Tc17) T cells were both increased in liver and peripheral blood mononuclear cells of CHB patients compared to those in HVs. CHB patients showed higher intrahepatic levels of CCL17 mRNA, CCL22 mRNA, CCR6 mRNA and CCR4 mRNA than HVs. The expression of CCR6 and CCR4 on the surface of Th17 and Tc17 cells in CHB patients was also significantly higher than that in HVs. Significant correlations existed between the CCR4/ CCR6 levels and both the alanine transaminase levels and HBV DNA loads. Contact between MoDCs and pBlue-HBV-transfected Huh7 cells induced the expression of CCL17 and CCL22 dependent on the dose of HBV DNA. However, CCL20 expression was lower in CHB patients than in HVs. Transwell experiments showed that upregulation of CCL17 and CCL22 enhanced the migration of IL-17 secreting T cells. Conclusions: Contact of HBV-transfected cells with MoDCs induces CCL17 andCCL22 chemokine production, which may favour the recruitment of Th17 and Tc17 cells to liver tissue in CHB. Our results reveal the mechanism of IL-17 secreting T cells recruitment to liver tissue and thus provide new immunotherapy targets for CHB patients.

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Section: Discussionsupporting

confidence: 82%

HBV promotes the recruitment of IL‐17 secreting T cells via chemokines CCL22 and CCL17

Zhang

Liu

Yang

et al. 2020

Liver International

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“…The present knowledge and understanding of the innate immune response of ACLF patients is limited. There are a number of specific issues left somewhat ambiguous, like whether a dysregulated innate immune response is the cause or outcome of Induces systemic inflammatory pathways, is associated with disease severity, short term mortality (34,123) IL-8 Neutrophil infiltration, liver inflammation, short term mortality (51,53,123) IL-10 Associated with poor prognosis and mortality (136) IL-17 Associated with clinical disease severity markers including INR and MELD, mortality, recruits proinflammatory cells, increases the expression of profibrogenic factor TGF-β, and inflammatory cytokines IL-6 and IL-23 (121,136,137) IL-22 Hepatoprotective, supports liver regeneration, attenuates bacterial infection (127,130) IL-23 Associated with clinical disease severity markers MELD, INR, prothrombin time, total bilirubin, and mortality (101,121) G-CSF and G-MSCF Reduces IFN-γ production, mobilizes CD34+ cells, improves clinical disease severity indices and survival in ACLF patients, reduces short term mortality, activates progenitors to promote differentiation and activation of monocytes and neutrophils (36,46,99,(138)(139)(140)(141) TGF-β Liver injury, disease severity, and poor survival in ACLF (122) VCAM-1, ICAM-1 Inflammation, short term mortality (36) ACLF. Few studies outlined abnormal innate immunity of ACLF patients which is associated with systemic inflammation, disease progression, and pathogenesis; however extensive research is required to find out the mechanisms responsible for disease severity and high mortality in these severely ill patients.…”

Section: Resultsmentioning

confidence: 99%

“…Systemic circulatory dysfunction and exacerbation of systemic inflammation leads to organ failure(s). (53,99,(117)(118)(119)(120)(121)(122)(123). The majority of these cytokines are related to the innate immune response such as leukocyte migration, particularly monocytes and macrophages, chemotaxis pathways, endothelial dysfunction, and subsequently induces systemic inflammation.…”

Section: Cytokine Responses During Aclfmentioning

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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“…In this study, there was no difference in levels of IL-12 and IL-23 in subjects with viral hepatitis compare to non-viral hepatitis. This could be caused by the presence of IL-12 and IL-23 in other types of hepatitis such as autoimmune hepatitis ( 35 ) and alcoholic hepatitis ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Association Between Serum IL-6, IL-10, IL-12, and IL-23 Levels and Severity of Liver Cirrhosis

Rey

Effendi-Ys

2021

Med Arch

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Background: Liver cirrhosis contributes to high liver-related mortality globally. Systemic inflammation mediated by immune cells contributes to the progression of liver cirrhosis. Growing evidence shows that several pro- and anti-inflammatory cytokines might have an important role in liver cirrhosis. Objective: To evaluate the association between serum IL-6, IL-10, IL-12, and IL-23 levels and severity of liver cirrhosis. Methods: This observational study was carried out at the Department of Internal Medicine, Universitas Sumatera Utara, Indonesia from March 2018 to August 2019. The severity of liver cirrhosis was assessed by using the Child-Pugh score. IL-6, IL-10, IL-12, and IL-23 levels, hepatitis and renal function were measured in all study subjects. Independent t-test and Mann-Whitney tests were conducted to observe differences between groups. Results: A total of 78 liver cirrhosis patients were enrolled, mean age was 50.6±11.4. Median serum IL-6, IL-10, IL-12, and IL-23 levels were 24.5(2.6-46.4)pg/ml, 2.1(0.4-9.3)pg/ml, 3.5(1.4-20.8)pg/ml and 20.3(9.2-218)pg/ml, respectively. A higher IL-6 level was associated with more severe liver cirrhosis (p=0.001) and the presence of hepatic encephalopathy (p=0.018). Higher IL-23 level was found in patients with no hepatic encephalopathy (p=0.049). There was no association between serum cytokines levels and hepatitis viral infection status. Conclusion: IL-6 is associated with the severity of liver cirrhosis.

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

Cited by 20 publications

References 42 publications

HBV promotes the recruitment of IL‐17 secreting T cells via chemokines CCL22 and CCL17

HBV promotes the recruitment of IL‐17 secreting T cells via chemokines CCL22 and CCL17

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

Association Between Serum IL-6, IL-10, IL-12, and IL-23 Levels and Severity of Liver Cirrhosis

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