Exogenous Interleukin-37 Alleviates Hepatitis with Reduced Dendritic Cells and Induced Regulatory T Cells in Acute Murine Cytomegalovirus Infection

Human cytomegalovirus (HCMV) infection is globally distributed, and the liver is one of the major targeting organs. So far, the mechanisms for cell and organ damage have not fully been elucidated and the treatments for the infection are mainly at symptoms. IL-37 has shown a protective role in certai...

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Main Authors: Yufei Ruan, Zhengwang Wen, Ke Chen, Jianan Xi, Bo Wu, Zhiyong Xu, Minzhi Jiang, Junling Zhang, Yiping Chen, Qi Liu
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2023/1462048
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author Yufei Ruan
Zhengwang Wen
Ke Chen
Jianan Xi
Bo Wu
Zhiyong Xu
Minzhi Jiang
Junling Zhang
Yiping Chen
Qi Liu
author_facet Yufei Ruan
Zhengwang Wen
Ke Chen
Jianan Xi
Bo Wu
Zhiyong Xu
Minzhi Jiang
Junling Zhang
Yiping Chen
Qi Liu
author_sort Yufei Ruan
collection DOAJ
description Human cytomegalovirus (HCMV) infection is globally distributed, and the liver is one of the major targeting organs. So far, the mechanisms for cell and organ damage have not fully been elucidated and the treatments for the infection are mainly at symptoms. IL-37 has shown a protective role in certain inflammatory diseases. In the present study, potential protective effect of exogenous IL-37 on murine cytomegalovirus- (MCMV-) infected hepatitis was evaluated through analyses of serum transaminases, the liver histopathology and cytokine expression, and functional state of dendritic cells (DCs) and regulatory T cells (Tregs). These analyses showed a significant decrease in serum transaminase levels and a lower Ishak histopathologic score at the early stage of MCMV-infected mice with exogenous IL-37 pretreatment. The frequencies of MHC-Ⅱ, CD40, CD80, and CD86 positive DCs in the liver and spleen were decreased significantly at 7 days postinfection (dpi) in MCMV-infected mice with IL-37 pretreatment when compared with those without the pretreatment, while the total number of DCs in the liver was reduced in IL-37-pretreated mice. The induction of Tregs in the spleen was enhanced at dpi 3 with IL-37 pretreatment in MCMV-infected mice. The mRNA expression levels of cytokines in the liver were decreased significantly (IL-1β, IL-6, IL-10, IL-4) or to some extent (TGF-β and TNF-α). The present study suggested that exogenous IL-37 can alleviate MCMV-infected hepatitis, likely through reduced DCs and induced Tregs with a weaker cytokine storm, demonstrating its potential value in clinical management for HCMV-infected hepatitis.
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spelling doaj-art-002b87fa0df84c76871dbe71de8e02df2025-02-03T05:44:35ZengWileyJournal of Immunology Research2314-71562023-01-01202310.1155/2023/1462048Exogenous Interleukin-37 Alleviates Hepatitis with Reduced Dendritic Cells and Induced Regulatory T Cells in Acute Murine Cytomegalovirus InfectionYufei Ruan0Zhengwang Wen1Ke Chen2Jianan Xi3Bo Wu4Zhiyong Xu5Minzhi Jiang6Junling Zhang7Yiping Chen8Qi Liu9Department of Pediatric Infectious DiseaseDepartment of Pediatric Infectious DiseaseDepartment of Pediatric Infectious DiseaseDepartment of Pediatric Infectious DiseaseSchool of Basic MedicineSchool of Basic MedicineSchool of Basic MedicineSchool of Basic MedicineDepartment of Pediatric Infectious DiseaseDepartment of Pediatric Infectious DiseaseHuman cytomegalovirus (HCMV) infection is globally distributed, and the liver is one of the major targeting organs. So far, the mechanisms for cell and organ damage have not fully been elucidated and the treatments for the infection are mainly at symptoms. IL-37 has shown a protective role in certain inflammatory diseases. In the present study, potential protective effect of exogenous IL-37 on murine cytomegalovirus- (MCMV-) infected hepatitis was evaluated through analyses of serum transaminases, the liver histopathology and cytokine expression, and functional state of dendritic cells (DCs) and regulatory T cells (Tregs). These analyses showed a significant decrease in serum transaminase levels and a lower Ishak histopathologic score at the early stage of MCMV-infected mice with exogenous IL-37 pretreatment. The frequencies of MHC-Ⅱ, CD40, CD80, and CD86 positive DCs in the liver and spleen were decreased significantly at 7 days postinfection (dpi) in MCMV-infected mice with IL-37 pretreatment when compared with those without the pretreatment, while the total number of DCs in the liver was reduced in IL-37-pretreated mice. The induction of Tregs in the spleen was enhanced at dpi 3 with IL-37 pretreatment in MCMV-infected mice. The mRNA expression levels of cytokines in the liver were decreased significantly (IL-1β, IL-6, IL-10, IL-4) or to some extent (TGF-β and TNF-α). The present study suggested that exogenous IL-37 can alleviate MCMV-infected hepatitis, likely through reduced DCs and induced Tregs with a weaker cytokine storm, demonstrating its potential value in clinical management for HCMV-infected hepatitis.http://dx.doi.org/10.1155/2023/1462048
spellingShingle Yufei Ruan
Zhengwang Wen
Ke Chen
Jianan Xi
Bo Wu
Zhiyong Xu
Minzhi Jiang
Junling Zhang
Yiping Chen
Qi Liu
Exogenous Interleukin-37 Alleviates Hepatitis with Reduced Dendritic Cells and Induced Regulatory T Cells in Acute Murine Cytomegalovirus Infection
Journal of Immunology Research
title Exogenous Interleukin-37 Alleviates Hepatitis with Reduced Dendritic Cells and Induced Regulatory T Cells in Acute Murine Cytomegalovirus Infection
title_full Exogenous Interleukin-37 Alleviates Hepatitis with Reduced Dendritic Cells and Induced Regulatory T Cells in Acute Murine Cytomegalovirus Infection
title_fullStr Exogenous Interleukin-37 Alleviates Hepatitis with Reduced Dendritic Cells and Induced Regulatory T Cells in Acute Murine Cytomegalovirus Infection
title_full_unstemmed Exogenous Interleukin-37 Alleviates Hepatitis with Reduced Dendritic Cells and Induced Regulatory T Cells in Acute Murine Cytomegalovirus Infection
title_short Exogenous Interleukin-37 Alleviates Hepatitis with Reduced Dendritic Cells and Induced Regulatory T Cells in Acute Murine Cytomegalovirus Infection
title_sort exogenous interleukin 37 alleviates hepatitis with reduced dendritic cells and induced regulatory t cells in acute murine cytomegalovirus infection
url http://dx.doi.org/10.1155/2023/1462048
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