Correlation of Interleukin-33/ST2 Receptor and Liver Fibrosis Progression in Biliary Atresia Patients

Overview

Journal Front Pediatr

Specialty Pediatrics

Date 2019 Oct 22

PMID 31632941

Citations 11

Authors

Jia Liu

Yifan Yang

Chao Zheng

Gong Chen

Zhen Shen

Shan Zheng

Rui Dong

Affiliations

Soon will be listed here.

Abstract

Biliary Atresia (BA) is a devastating pediatric liver disease and characterized by aggressive liver fibrosis progression. The Interleukin-33 (IL-33)/ST2 receptor signaling axis has been demonstrated to be involved in several autoimmune and liver diseases. Since immune dysregulation is a contributor to BA pathogenesis, we aimed to investigate the role of IL-33/ST2 receptor in the progression of liver fibrosis in BA patients. The study included 36 BA patients (18 good- and 18 poor-prognosis BA patients); and 8 cholestasis infants as the control group. Patients' information and clinical data were retrospectively collected and compared. Liver fibrosis stage was determined by Masson's trichrome staining. Gene expression levels of IL-33, ST2 receptor, and TFG-β1 were detected by quantitative real-time PCR. MC count, IL-33, TGF-β1, and Interleukin-13 (IL-13) expressions were evaluated by immunohistochemistry. Serum IL-33 expression level was detected by enzyme-linked immunosorbent assay. Co-expression of MC and ST2 receptor was detected by immunofluorescence. mast cell was cultured with IL-33 stimulation, and ST2 receptor and TGF-β1 expressions were detected. Compared with cholestasis control, BA patients had significantly higher GGT level and Masson score. Expression levels of IL-33, TGF-β1, and IL-13 were significantly increased in BA patients compared to control group, especially in poor-prognosis BA patients. Co-expression of ST2 receptor and MC was found in BA liver tissues. The MC count was markedly higher in BA patients especially in poor-prognosis subgroup. Serum IL-33 level was significantly elevated in poor-prognosis BA patients and related to a higher Masson score. mast cell culture exhibited significant upregulation of ST2 receptor and TGF-β1 mRNA expression after IL-33 stimulation. IL-33/ST2 receptor signaling axis is correlated with liver fibrosis progression in BA patients, and mast cells participates in this process. These indicate potential prognostic evaluation factors for BA patients and can help in the postoperative management to achieve better long-term prognosis in BA patients.

Citing Articles

Biliary atresia.

Tam P, Wells R, Tang C, Lui V, Hukkinen M, Luque C Nat Rev Dis Primers. 2024; 10(1):47.

PMID: 38992031 DOI: 10.1038/s41572-024-00533-x.

The role of interleukin-33 in organ fibrosis.

Di Carmine S, Scott M, McLean M, McSorley H Discov Immunol. 2024; 1(1):kyac006.

PMID: 38566909 PMC: 10917208. DOI: 10.1093/discim/kyac006.

Relationship between the expression levels of CD4+ T cells, IL-6, IL-8 and IL-33 in the liver of biliary atresia and postoperative cholangitis, operative age and early jaundice clearance.

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PMID: 36242601 DOI: 10.1007/s00383-022-05258-0.

Exploring the role of mast cells in the progression of liver disease.

Huang S, Wu H, Luo F, Zhang B, Li T, Yang Z Front Physiol. 2022; 13:964887.

PMID: 36176778 PMC: 9513450. DOI: 10.3389/fphys.2022.964887.

IL13 and periostin in active fibrogenic areas of the extrahepatic bile ducts in biliary atresia patients.

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PMID: 36149445 DOI: 10.1007/s00383-022-05238-4.

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