Polarization of Monocytic Myeloid-Derived Suppressor Cells by Hepatitis B Surface Antigen Is Mediated via ERK/IL-6/STAT3 Signaling Feedback and Restrains the Activation of T Cells in Chronic Hepatitis B Virus Infection

Fang, Zhong; Jin, Li; Yu, Xiaoyu; Zhang, Dandan; Ren, Guangxu; Shi, Bisheng; Wang, Cong; Kosinska, Anna D.; Wang, Sen; Zhou, Xiaohui; Kozlowski, Maya; Hu, Yunwen

doi:10.4049/jimmunol.1501362

Cited by 84 publications

(112 citation statements)

References 45 publications

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“…Other reports also confirm that monocytes can be reprogrammed into Mo-MDSCs by demonstrating that peripheral blood monocytes can serve as precursors to Mo-MDSCs under specific conditions in vitro [106, 107, 120, 125, 126]. This further indicates that monocytes can indeed be the source of Mo-MDSCs.…”

Section: Reprogramming Of Monocytesmentioning

confidence: 69%

On the origin of myeloid-derived suppressor cells

2016

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Myeloid-derived suppressor cells (MDSCs) have a strong immunosuppressive character that allows them to regulate immune responses and hinder overt inflammatory responses. In cancer, this leads to tumor immune evasion and disease progression. MDSCs come in at least two forms: monocytic (Mo-MDSCs) and granulocytic (G-MDSCs). The classical definition of MDSCs as immature myeloid cells blocked from differentiating has been challenged by recent studies suggesting that Mo-MDSCs and G-MDSCs may represent monocytes and granulocytes that have acquired immunosuppressive properties. The molecular mechanism behind their generation and their true origins are now widely debated. In this review we discuss the different proposed mechanisms of the generation of both types of MDSCs, with a special focus on human MDSCs in cancer.

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Section: Reprogramming Of Monocytesmentioning

confidence: 69%

On the origin of myeloid-derived suppressor cells

2016

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“…The factors involved in driving MDSC expansion and/or differentiation during viral infections, including cytokines and chemokines, remain less clear. During chronic HBV infection, the frequency of MDSCs correlated with the level of hepatitis B surface Ag (HBsAg), and culture of human PBMCs with HBsAg led to differentiation of these cells to MDSCs in an ERK/IL-6/STAT3 signaling-dependent manner, indicating that viral antigen may play a role in triggering the expansion of MDSCs (39).…”

Section: Factors Involved In Mdsc Expansionmentioning

confidence: 99%

The Role of Myeloid-Derived Suppressor Cells in Viral Infection

2017

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Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature myeloid cells that are well described as potent immune regulatory cells during human cancer and murine tumor models. Reports of MDSCs during viral infections remain limited, and their association with immunomodulation of viral diseases is still being defined. Here, we provide an overview of MDSCs or MDSC-like cells identified during viral infections, including murine viral models and human viral diseases. Understanding the similarities and/or differences of virally induced versus tumor-derived MDSCs will be important for designing future immunotherapeutic approaches.

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“…A recent finding revealed that HBsAg could promote differentiation of monocytes into M-MDSCs which could suppress HBV-specific T cell responses [36]. MDSC was also found to promote CD8 + T cell exhaustion by γδT cells in HBVcarrier immunocompetent mice [37].…”

Section: Discussionmentioning

confidence: 99%

Expansion of HLA-G-Expressing Myeloid-Derived Suppressor Cells in Patients with Chronic Hepatitis B Virus Infection

Lu¹,

Li²,

Lin³

et al. 2017

J Antivir Antiretrovir

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Both human leukocyte antigen-G (HLA-G) and myeloid-derived suppressor cells (MDSCs) was associated with the pathogenesis of infectious diseases. Whether peripheral MDSCs express HLA-G during virus infection remains unknown. We investigated the frequency of HLA-G + MDSCs and its subsets in patients infected with chronic hepatitis B (CHB). In this study, frequencies of peripheral MDSCs (Lin1-HLA-DR-CD33 + CD11b + ) and HLA-G expressing subsets from 50 CHB patients and 27 normal controls were analyzed using flow cytometry. Data revealed the median percentage of MDSCs was not significantly different between the CHB patients and controls (0.30% vs. 0.29%; p=0.884). Among MDSCs, similar frequency was observed for CD14+ monocytic MDSC (mMDSCs; 31.25% vs. 23.35%; p=0.063) and CD15 + granulocytic MDSC (gMDSCs; 22.60% vs. 21.55%; p=0.558) between the two groups. However, HLA-G + MDSCs was significantly increased in CHB patients compared with that of controls (3.30% vs. 0.50%; p<0.001). Furthermore, both HLA-G + mMDSCs (0.99% vs. 0.00%; p<0.001) and HLA-G + gMDSC (0.78% vs. 0.00%; p<0.001) were also dramatically increased in CHB patients. Particularly, HLA-G + gMDSC was inversely correlated to the viral DNA loads and significantly increased in HBeAb positive patients. Summary, this work reports for the first time HLA-G + MDSCs, a new population of peripheral MDSCs, were expanded in CHB patients; however, its clinical relevance yet to be further explored.

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Polarization of Monocytic Myeloid-Derived Suppressor Cells by Hepatitis B Surface Antigen Is Mediated via ERK/IL-6/STAT3 Signaling Feedback and Restrains the Activation of T Cells in Chronic Hepatitis B Virus Infection

Cited by 84 publications

References 45 publications

On the origin of myeloid-derived suppressor cells

On the origin of myeloid-derived suppressor cells

The Role of Myeloid-Derived Suppressor Cells in Viral Infection

Expansion of HLA-G-Expressing Myeloid-Derived Suppressor Cells in Patients with Chronic Hepatitis B Virus Infection

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