Evidence map›Paper›PMID 41419948›Full record

ArticleJournal of translational medicine2025

IL-21 attenuates liver inflammation by enhancing myeloid-derived suppressor cells immunosuppressive function in chronic HBV infection.

Xiaoyi Li, Zihan Jin, Meihan Pan, Zheyu Dong, Junlin Chen, Zhipeng Liu, Hongjie Chen, Guofu Ye, Shihong Zhong, Weiying He and 3 more

Abstract read
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Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Xiaoyi Li *Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Multi-Organ Injury Prevention and Treatment; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology, No.1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Zihan Jin *Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Multi-Organ Injury Prevention and Treatment; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology, No.1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Meihan Pan *Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Multi-Organ Injury Prevention and Treatment; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology, No.1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Zheyu Dong *Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Multi-Organ Injury Prevention and Treatment; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology, No.1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Junlin ChenDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Multi-Organ Injury Prevention and Treatment; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology, No.1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Zhipeng LiuDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Multi-Organ Injury Prevention and Treatment; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology, No.1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Hongjie ChenDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Multi-Organ Injury Prevention and Treatment; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology, No.1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Guofu YeDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Multi-Organ Injury Prevention and Treatment; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology, No.1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Shihong ZhongDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Multi-Organ Injury Prevention and Treatment; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology, No.1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Weiying HeDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Multi-Organ Injury Prevention and Treatment; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology, No.1838 North Guangzhou Avenue, Guangzhou, 510515, China.
Libo TangDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Multi-Organ Injury Prevention and Treatment; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology, No.1838 North Guangzhou Avenue, Guangzhou, 510515, China. tanglibosmu@foxmail.com.
GuiRong RaoCentral Laboratory of Air Force Hospital in the Southern Theater, Guangzhou, 510602, Guangdong Province, PR China. raogr@126.com.
Yongyin LiDepartment of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Multi-Organ Injury Prevention and Treatment; Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology, No.1838 North Guangzhou Avenue, Guangzhou, 510515, China. yongyinli@foxmail.com.ORCID 0000-0001-6303-7642

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChronic hepatitis B virus (HBV) infection progression is closely associated with repeated inflammatory liver injury. Myeloid-derived suppressor cells (MDSCs), known to suppress inflammatory responses during hepatitis, may play a protective role in mitigating liver damage; nevertheless, the precise functional specialization of MDSC subpopulations and the critical regulator in controlling their suppressive capacity remain incompletely understood. This study investigates the immunoregulatory role of IL-21, a pleiotropic immunomodulatory cytokine, in modulating MDSC function and its implications for HBV-associated liver inflammation prognosis.

methodsThe frequencies of peripheral and intrahepatic MDSCs, along with serum IL-21 levels, in patients with chronic HBV infection were measured with freshly isolated samples. C57BL/6 mice carrying pAAV-HBV1.2 plasmids was established to explore the effect of IL-21 on aminotransferase levels and MDSC function.

resultsPatients with chronic HBV infection demonstrated significantly elevated frequencies of circulating MDSCs compared to healthy controls. Of note, the granulocytic MDSCs (gMDSCs) were markedly more abundant in hepatic tissues than in peripheral blood. Strikingly, a significant inverse correlation was observed between circulating gMDSC frequencies and serum ALT levels specifically in patients with elevated serum IL-21 concentrations, whereas this correlation was absent in the low IL-21 subgroup. In vitro functional assays demonstrated that exogenous IL-21 potentiated the immunosuppressive capacity of MDSCs, significantly attenuating IFN-γ production in co-cultured T cells. Consistent with these findings, hydrodynamic injection of IL-21 plasmid in an HBV mouse model resulted in significantly reduced serum ALT levels concomitant with enhanced arginase I expression in hepatic MDSCs.

conclusionsThese results reveal that IL-21 enhances MDSC-mediated immunosuppression, implicating this regulatory axis in the attenuation of hepatic inflammation during chronic HBV infection. These findings provide a novel perspective on the involvement of IL-21 in the negative regulation of intrahepatic inflammation and provide a novel perspective on the role of IL-21 in developing immunotherapeutic strategies to optimize available anti-inflammatory treatments in chronic HBV infection.

Indexed as

Hepatitis B, ChronicImmune ToleranceImmunosuppression TherapyInflammationInterleukinsLiverMyeloid-Derived Suppressor CellsAdultAnimalsFemaleHepatitis B virusHumansInterleukin-21MaleMiceMice, Inbred C57BLInterleukin-21InterleukinsHepatitis B virusImmunosuppressive activityInterleukin 21Intrahepatic inflammationMyeloid-derived suppressor cells

Identifiers

PMID41419948
PMCPMC12717690

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.