Interleukin-33 Promotes Disease Progression in Patients with Primary Biliary Cirrhosis

Sun, Yu; Zhang, Jiyuan; Lv, Sa; Wang, Huan; Gong, Ming; Du, Ning; Liu, Honghong; Zhang, Ning; Jing, Jing; Zhou, Chao; Zhang, Fan; Wang, Zongren

doi:10.1620/tjem.234.255

Cited by 18 publications

(20 citation statements)

References 22 publications

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“…30 In our present work, we demonstrate that IL-33 is elevated in cirrhotic livers, and ILC2s are upregulated, along with hepatic fibrogenesis. 31 Furthermore, ST2-deficient mice reveal that IL-33/ST2 is both required and sufficient for BDL-induced liver inflammation and fibrosis. Intraperitoneal injection of rmIL-33 induces liver inflammation in naive BL6 mice, as reported.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-33 drives hepatic fibrosis through activation of hepatic stellate cells

Tan¹,

Liu²,

Jiang³

et al. 2017

Cell Mol Immunol

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Section: Discussionmentioning

confidence: 99%

Interleukin-33 drives hepatic fibrosis through activation of hepatic stellate cells

Tan¹,

Liu²,

Jiang³

et al. 2017

Cell Mol Immunol

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“…Recent studies reported a crucial role for IL-33 in the pathology of immune-mediated liver diseases (22)(23)(24). During immunemediated hepatitis, highly elevated IL-33 levels correlated with severe liver inflammation and tissue damage.…”

Section: Discussionmentioning

confidence: 99%

“…ILC2-derived IL-5 controls eosinophil maintenance and infiltration (19,20), whereas IL-13 induces airway hyper-responsiveness (15) and contributes to parasite expulsion (21). Previous studies have implicated IL-33 in the pathogenesis of liver diseases such as chronic viral infection (22), primary biliary cirrhosis (23), and liver fibrosis (17,24). IL-33 is expressed by hepatocytes during immune-mediated hepatitis (25), but whether IL-33-elicited ILC2s contribute to disease pathogenesis has not been studied yet.…”

mentioning

confidence: 99%

A Proinflammatory Role of Type 2 Innate Lymphoid Cells in Murine Immune-Mediated Hepatitis

Neumann

Karimi

Meiners

et al. 2017

The Journal of Immunology

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Type 2 innate lymphoid cells (ILC2) mediate inflammatory immune responses in the context of diseases triggered by the alarmin IL-33. In recent years, IL-33 has been implicated in the pathogenesis of immune-mediated liver diseases. However, the immunoregulatory function of ILC2s in the inflamed liver remains elusive. Using the murine model of Con A-induced immune-mediated hepatitis, we showed that selective expansion of ILC2s in the liver was associated with highly elevated hepatic IL-33 expression, severe liver inflammation, and infiltration of eosinophils. CD4 T cell-mediated tissue damage and subsequent IL-33 release were responsible for the activation of hepatic ILC2s that produced the type 2 cytokines IL-5 and IL-13 during liver inflammation. Interestingly, ILC2 depletion correlated with less severe hepatitis and reduced accumulation of eosinophils in the liver, whereas adoptive transfer of hepatic ILC2s aggravated liver inflammation and tissue damage. We further showed that, despite expansion of hepatic ILC2s, 3-d IL-33 treatment before Con A challenge potently suppressed development of immune-mediated hepatitis. We found that IL-33 not only activated hepatic ILC2s but also expanded CD4 Foxp3 regulatory T cells (Treg) expressing the IL-33 receptor ST2 in the liver. This Treg subset also accumulated in the liver during resolution of immune-mediated hepatitis. In summary, hepatic ILC2s are poised to respond to the release of IL-33 upon liver tissue damage through expression of type 2 cytokines thereby participating in the pathogenesis of immune-mediated hepatitis. Inflammatory activity of ILC2s might be regulated by IL-33-elicited ST2 Tregs that also arise in immune-mediated hepatitis.

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“…IL‐33 has been reported to correlate with liver injury in patients with primary biliary cirrhosis (PBC) . Notably, serum levels of IL‐33 were closely associated with the degree of liver injury in patients with hepatitis B virus (HBV) infection .…”

mentioning

confidence: 99%

“…(11) IL-33 has been reported to correlate with liver injury in patients with primary biliary cirrhosis (PBC). (12) Notably, serum levels of IL-33 were closely associated with the degree of liver injury in patients with hepatitis B virus (HBV) infection. (13) Moreover, the evaluation of dynamic changes in sST2 levels in HBV acute-on-chronic liver failure showed that serum sST2 levels increased over time in patients who died during follow-up but decreased in those who survived.…”

mentioning

confidence: 99%

Interleukin‐33/ST2‐Mediated Inflammation Plays a Critical Role in the Pathogenesis and Severity of Type I Autoimmune Hepatitis

Abe¹,

Takahashi²,

Fujita³

et al. 2019

Hepatol Commun

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Interleukin (IL)‐33 was recently described as a new member of the IL‐1 family; members of this family have proinflammatory activity. IL‐33 and its soluble receptor ST2 (sST2) have been implicated in the pathogenesis of autoimmune diseases. This study investigated serum IL‐33 and sST2 in type I autoimmune hepatitis (AIH) and the relationship of these molecules with clinical and pathologic parameters. Subjects included 65 patients with AIH who were diagnosed in our hospital. The control population included 17 healthy individuals and 36 patients with primary biliary cholangitis (PBC). Mean age at AIH diagnosis was 55.5 years, and the male‐to‐female ratio was 6:59. Serum IL‐33 and sST2 levels were significantly higher in patients with AIH than in those with PBC or controls. Importantly, immunohistochemistry revealed high IL‐33 expression in liver sections from patients with AIH. In particular, serum IL‐33 and sST2 levels were significantly higher in acute‐onset AIH than in chronic‐onset AIH. Serum IL‐33 levels were positively correlated with serum total bilirubin (TB), alanine aminotransferase (ALT), and necroinflammatory activity in AIH. We performed multivariate logistic regression analysis and found serum IL‐33 levels to be independent factors for severe activity. Serum sST2 levels were positively correlated with serum TB and ALT and negatively correlated with serum albumin and prothrombin time in AIH. In particular, serum sST2 levels were significantly higher in severe symptoms of AIH. Serum IL‐33 and sST2 levels in patients with AIH responsive to treatment with prednisolone were significantly decreased after treatment. Interestingly, serum IL‐33 level was associated with a significantly increased risk of relapse. Conclusion: IL‐33/ST2 may play an important role in the pathogenesis and severity of AIH and may be a promising target for AIH therapy.

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Interleukin-33 Promotes Disease Progression in Patients with Primary Biliary Cirrhosis

Cited by 18 publications

References 22 publications

Interleukin-33 drives hepatic fibrosis through activation of hepatic stellate cells

Interleukin-33 drives hepatic fibrosis through activation of hepatic stellate cells

A Proinflammatory Role of Type 2 Innate Lymphoid Cells in Murine Immune-Mediated Hepatitis

Interleukin‐33/ST2‐Mediated Inflammation Plays a Critical Role in the Pathogenesis and Severity of Type I Autoimmune Hepatitis

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