The Relationship between Hepatic Myeloid-Derived Suppressor Cells and Clinicopathological Parameters in Patients with Chronic Liver Disease

Zhou, Zhijia; Lai, Penghua; Zhang, Shaoliang; Wang, Yujie; Qu, Ning; Lü, Dawei; Gao, Liangqin; Xu, Lingxia; Yang, Yanmiao; Zhang, Ting; Sun, Xue Li; Zheng, Xiaoting; Liu, Yaoyu; Liang, Huiqing; Chen, Shaodong

doi:10.1155/2021/6612477

Cited by 8 publications

(5 citation statements)

References 40 publications

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“…ROS production in patient-derived PMN-MDSCs is aggravated under hyperglycemic conditions [ 62 ]. MDSCs in BALF correlated with airflow limitation severity in COPD patients [ 63 ], accumulated in the human liver with NAFLD [ 64 ], and correlated positively with the clinical parameters alanine transaminase (ALT), aspartate aminotransferase (AST) and globulin [ 65 ]. Moreover, S. aureus infection in a diabetic mouse model causes an increase in LDN and NET production compared to infected nondiabetic mice [ 59 ].…”

Section: Neutrophil Heterogeneity In Chronic Inflammationmentioning

confidence: 99%

Neutrophils in chronic inflammatory diseases

2022

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Chronic inflammation is a component of many disease conditions that affect a large group of individuals worldwide. Chronic inflammation is characterized by persistent, low-grade inflammation and is increased in the aging population. Neutrophils are normally the first responders to acute inflammation and contribute to the resolution of inflammation. However, in chronic inflammation, the role of neutrophils is less well understood and has been described as either beneficial or detrimental, causing tissue damage and enhancing the immune response. Emerging evidence suggests that neutrophils are important players in several chronic diseases, such as atherosclerosis, diabetes mellitus, nonalcoholic fatty liver disease and autoimmune disorders. This review will highlight the interaction of neutrophils with other cells in the context of chronic inflammation, the contribution of neutrophils to selected chronic inflammatory diseases, and possible future therapeutic strategies.

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Section: Neutrophil Heterogeneity In Chronic Inflammationmentioning

confidence: 99%

Neutrophils in chronic inflammatory diseases

2022

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“…An increase in MDSCs acts as a potent inhibitor of T cell-mediated immunity in autoimmune hepatitis and cancer, which is attributed to the production of Arginase1, ROS, iNOS, and IL-10 (21,22). An increase in hepatic CD11b + CD33 + MDSCs positively correlated with liver fibrosis and also linearly correlated with the tumor volume (23). Furthermore, peripheral blood MDSCs were also increased in cirrhosis and HCC patients (24).…”

Section: Discussionmentioning

confidence: 97%

Granulocyte-Macrophage Colony-Stimulating Factor Modulates Myeloid-Derived Suppressor Cells and Treg Activity in Decompensated Cirrhotic Patients With Sepsis

et al. 2022

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BackgroundDecompensated cirrhosis patients are more prone to bacterial infections. Myeloid-derived suppressor cells (MDSCs) expand in sepsis patients and disrupt immune cell functions. Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy helps in restoring immune cell functions and resolving infections. Its role in MDSC modulation in cirrhosis with sepsis is not well understood.MethodsA total of 164 decompensated cirrhotic—62 without (w/o), 72 with sepsis, and 30 with sepsis treated with GM-CSF—and 15 healthy were studied. High-dimensional flow cytometry was performed to analyze MDSCs, monocytes, neutrophils, CD4 T cells, and Tregs at admission and on days 3 and day 7. Ex vivo co-cultured MDSCs with T cells were assessed for proliferation and apoptosis of T cells and differentiation to Tregs. Plasma factors and mRNA levels were analyzed by cytokine-bead assay and qRT-PCR.ResultsFrequencies of MDSCs and Tregs were significantly increased (p = 0.011 and p = 0.02) with decreased CD4 T cells (p = 0.01) in sepsis than w/o sepsis and healthy controls (HCs) (p = 0.000, p = 0.07, and p = 0.01) at day 0 and day 7. In sepsis patients, MDSCs had increased IL-10, Arg1, and iNOS mRNA levels (p = 0.016, p = 0.043, and p = 0.045). Ex vivo co-cultured MDSCs with T cells drove T-cell apoptosis (p = 0.03, p = 0.03) with decreased T-cell proliferation and enhanced FOXP3+ expression (p = 0.044 and p = 0.043) in sepsis compared to w/o sepsis at day 0. Moreover, blocking the MDSCs with inhibitors suppressed FOXP3 expression. GM-CSF treatment in sepsis patients significantly decreased MDSCs and FOXP3+ Tregs but increased CD4 T-cell functionality and improved survival.ConclusionMDSCs have an immunosuppressive function by expanding FOXP3+ Tregs and inhibiting CD4+ T-cell proliferation in sepsis. GM-CSF treatment suppressed MDSCs, improved T-cell functionality, and reduced Tregs in circulation.

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“…Increase in MDSCs acts as a potent inhibitor of T-cell-mediated immunity in autoimmune hepatitis and cancer, which is attributed to the production of Arginase1, ROS, iNOS, and IL-10[18 -19]. Increase in hepatic CD11b + CD33 + MDSCs positively correlated with liver brosis stages while MDSC number linearly correlated with the tumor volume [20]. Further, M-MDSCs were strongly correlated with raised ALT, AST, and decreased T-cell proliferation [21].…”

Section: Discussionmentioning

confidence: 99%

GMCSF modulates Myeloid derived suppressor cells and Tregs activity in decompensated cirrhotic patients with sepsis

Sehgal

Maiwall

Rajan

et al. 2021

Preprint

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Background Decompensated cirrhosis patients are more prone to bacterial infections. Myeloid derived suppressor cells (MDSCs) expand in sepsis patients and disrupt immune cell functions. GM-CSF therapy helps in restoring immune cell functions and resolve infections. Its role in MDSCs modulation in cirrhotic with sepsis is not well understood. Methods 164 decompensated cirrhotic; 62 without(w/o), 72 with sepsis and 30 with sepsis treated with GM-CSF and 15 healthy were studied. High-dimensional flow cytometry was performed to analyse MDSCs, monocytes, neutrophils, CD4 T-cells and Tregs at admission, day3 and 7. Ex-vivo co-cultured MDSCs with T-cells were assessed for proliferation and apoptosis of T-cells, differentiation to T-regs. Plasma factors and mRNA levels were analysed by cytokine-bead assay and qRT-PCR. Results Frequency of MDSCs and T-regs were significantly increased (p=0.011, and p=0.02) with decreased CD4 T-cells(p=0.01) in sepsis than without sepsis and HC (p=0.000, p=0.07 and p=0.01) at day0, and day7. In sepsis patients, MDSCs had increased IL-10, Arg1 and iNOS mRNA levels (p=0.016, p=0.049 and p=0.06). Ex-vivo co-cultured MDSCs with T-cells drove T-cell apoptosis (p=0.03, p=0.03) with decreased T-cell proliferation and enhanced FOXP3+ expression (p=0.05 and p=0.05) in sepsis compared to no sepsis at day0. Moreover, blocking the MDSCs with inhibitors suppressed FOXP3 expression. GM-CSF treatment in sepsis patients significantly decreased MDSCs and FOXP3+Tregs but increased CD4 T-cell functionality and improved survival. Conclusion MDSCs have immunosuppressive function by expanding FOXP3+ Tregs and inhibiting CD4+ T-cell proliferation in sepsis. GM-CSF treatment suppressed MDSCs, improved T-cell functionality and reduced Tregs in circulation.

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The Relationship between Hepatic Myeloid-Derived Suppressor Cells and Clinicopathological Parameters in Patients with Chronic Liver Disease

Cited by 8 publications

References 40 publications

Neutrophils in chronic inflammatory diseases

Neutrophils in chronic inflammatory diseases

Granulocyte-Macrophage Colony-Stimulating Factor Modulates Myeloid-Derived Suppressor Cells and Treg Activity in Decompensated Cirrhotic Patients With Sepsis

GMCSF modulates Myeloid derived suppressor cells and Tregs activity in decompensated cirrhotic patients with sepsis

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