Mucosal-associated invariant T cells promote ductular reaction through amphiregulin in biliary atresia

Xiao, Man-Huan; Wu, Sihan; Liang, Peishi; Ma, Dong; Zhang, Jiang; Chen, Huadong; Zhong, Zhihai; Liu, Juncheng; Jiang, Hong; Feng, Xuyang; Luo, Zhenhua

doi:10.1016/j.ebiom.2024.105138

Cited by 4 publications

(2 citation statements)

References 69 publications

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“…The stage of liver brosis at the time of Kasai surgery signi cantly in uences prognosis [22]. According to the Metavir standard, F2 or F3 indicates advanced liver brosis with reversible tissue structure, whereas F4 denotes cirrhosis, characterized by a lack of accurate non-invasive serum biomarkers and asymptomatic nature [23,24].…”

Section: Discussionmentioning

confidence: 99%

Expression and clinical significance of MMP-13 in the liver of children with biliary atresia

Xiong,

Zheng,

Liu

et al. 2024

Preprint

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Objective: This study aims to investigate the correlation between matrix metalloproteinase-13 (MMP-13) expression in the liver of patients with biliary atresia and various factors including liver fibrosis stage, liver function indices, serological models of liver fibrosis, and the rate of jaundice resolution post-surgery. This investigation seeks to establish a basis for predicting liver fibrosis progression and the prognosis of biliary atresia. Methods: Liver tissues from 56 children with biliary atresia and 12 with congenital biliary dilatation treated at the Affiliated Hospital of Zunyi Medical University were selected, forming the study's observation and control groups, respectively. Liver fibrosis was staged using the Metavir scoring system following hematoxylin and eosin (HE) staining. Immunohistochemistry was utilized to detect MMP-13 expression in liver tissue, followed by semi-quantitative analysis. Expression levels were compared across different stages of fibrosis and correlated with liver function tests and the serological models APRI, GPR, and S index. Patients were categorized into non-progressive and progressive liver fibrosis groups, as well as non-cirrhotic and cirrhotic groups, based on fibrosis stage. The predictive value of MMP-13 for liver fibrosis stages was assessed using the area under the receiver operating characteristic (ROC) curve and the Youden index was applied to determine the optimal cut-off value. Additionally, the relationship between the age at surgery and MMP-13 expression, as well as the correlation between MMP-13 expression and the rate of jaundice resolution after Kasai surgery, was analyzed. Results: Among the 56 children with biliary atresia, liver fibrosis stages were distributed as follows: F0 (0 cases), F1 (0 cases), F2 (7 cases), F3 (11 cases), and F4 (38 cases). The control group of 12 children with congenital biliary dilatation all had F0 fibrosis. MMP-13 protein expression was significantly higher in the F2, F3, and F4 stages compared to the control group (P < 0.001), with expression intensifying as fibrosis progressed. The ROC curve analysis indicated a high predictive accuracy of MMP-13 for progressive liver fibrosis (AUC = 0.942) and cirrhosis (AUC = 0.721). MMP-13 expression showed positive correlations with biochemical markers of cholestasis and negative correlations with prothrombin activity. No significant correlations were found with other liver function tests. MMP-13 expression was also positively correlated with the GPR and S index but not with APRI. In children undergoing Kasai surgery, older age at surgery was associated with higher MMP-13 expression, and higher MMP-13 expression was linked to a lower rate of jaundice resolution post-surgery. Conclusion: Elevated MMP-13 expression in the liver of children with biliary atresia correlates with the progression of liver fibrosis and serological fibrosis markers. It serves as a potential prognostic indicator for post-surgical liver fibrosis in these patients. Furthermore, age at the time of surgery influences MMP-13 expression levels and the efficacy of jaundice resolution following surgery.

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Section: Discussionmentioning

confidence: 99%

Expression and clinical significance of MMP-13 in the liver of children with biliary atresia

Xiong,

Zheng,

Liu

et al. 2024

Preprint

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“…This was demonstrated in mouse models, where Mr1-/- NOD mice exhibited increased intestinal permeability compared to Mr1+/+ NOD mice, indicating a protective role of MR1-mediated MAIT cells in maintaining intestinal homeostasis ( 60 ). Similarly, in vitro human cholangiocyte cell line H69 wound healing assay, MAIT cells showed wound healing characteristics dependent on MR1-antigen-TCR interaction conduction ( 81 ). Direct application of 5-OP-RU on injured skin was also sufficient to expand MAIT cells and accelerate tissue repair in mice ( 10 ).…”

Section: Maintenance and Triggering Of Tissue-protective Functionsmentioning

confidence: 99%

Insights into the tissue repair features of MAIT cells

Gao,

Zhao

2024

Front. Immunol.

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Mucosa-associated invariant T (MAIT) cells are a subset of innate-like non-conventional T cells characterized by multifunctionality. In addition to their well-recognized antimicrobial activity, increasing attention is being drawn towards their roles in tissue homeostasis and repair. However, the precise mechanisms underlying these functions remain incompletely understood and are still subject to ongoing exploration. Currently, it appears that the tissue localization of MAIT cells and the nature of the diseases or stimuli, whether acute or chronic, may induce a dynamic interplay between their pro-inflammatory and anti-inflammatory, or pathogenic and reparative functions. Therefore, elucidating the conditions and mechanisms of MAIT cells’ reparative functions is crucial for fully maximizing their protective effects and advancing future MAIT-related therapies. In this review, we will comprehensively discuss the establishment and potential mechanisms of their tissue repair functions as well as the translational application prospects and current challenges in this field.

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Central role for cholangiocyte pathobiology in cholestatic liver diseases

Jalan-Sakrikar,

Guicciardi,

O’Hara

et al. 2024

Hepatology

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Cholangiopathies comprise a spectrum of chronic intrahepatic and extrahepatic biliary tract disorders culminating in progressive cholestatic liver injury, fibrosis, and often cirrhosis and its sequela. Treatment for these diseases is limited, and collectively, they are one of the therapeutic “black boxes” in clinical hepatology. The etiopathogenesis of the cholangiopathies likely includes disease-specific mediators but also common cellular and molecular events driving disease progression (eg, cholestatic fibrogenesis, inflammation, and duct damage). The common pathways involve cholangiocytes, the epithelial cells lining the intrahepatic and extrahepatic bile ducts, which are central to the pathogenesis of these disorders. Current information suggests that cholangiocytes function as a signaling “hub” in biliary tract-associated injury. Herein, we review the pivotal role of cholangiocytes in cholestatic fibrogenesis, focusing on the crosstalk between cholangiocytes and portal fibroblasts and HSCs. The proclivity of these cells to undergo a senescence-associated secretory phenotype, which is proinflammatory and profibrogenic, and the intrinsic intracellular activation pathways resulting in the secretion of cytokines and chemokines are reviewed. The crosstalk between cholangiocytes and cells of the innate (neutrophils and macrophages) and adaptive (T cells and B cells) immune systems is also examined in detail. The information will help consolidate information on this topic and guide further research and potential therapeutic strategies for these diseases.

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Mucosal-associated invariant T cells promote ductular reaction through amphiregulin in biliary atresia

Cited by 4 publications

References 69 publications

Expression and clinical significance of MMP-13 in the liver of children with biliary atresia

Expression and clinical significance of MMP-13 in the liver of children with biliary atresia

Insights into the tissue repair features of MAIT cells

Central role for cholangiocyte pathobiology in cholestatic liver diseases

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