scholarly journals A Novel CD48-Based Analysis of Sepsis-Induced Mouse Myeloid-Derived Suppressor Cell Compartments

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Bei Jia ◽  
Chenchen Zhao ◽  
Guoli Li ◽  
Yaxian Kong ◽  
Yaluan Ma ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Cecal Ligation ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Identification System ◽  
Disease States ◽  
Myeloid Derived Suppressor Cell ◽  
Reporter Mice ◽  
Novel Strategy ◽  
Green Fluorescent

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous subset of cells that expands dramatically in many disease states and can suppress T-cell responses. MDSCs mainly include monocytic and granulocytic subpopulations that can be distinguished in mice by the expression of Ly6G and Ly6C cell surface markers. This identification system has been validated in experimental tumor models, but not in models of inflammation-associated conditions such as sepsis. We challenged growth factor independent 1 transcription repressor green fluorescent protein (Gfi1:GFP) knock-in reporter mice with cecal ligation and puncture surgery and found that CD11b+Ly6GlowLy6Chigh MDSCs in this sepsis model comprised both monocytic and granulocytic MDSCs. The evidence that conventional Ly6G/Ly6C marker analysis may not be suited to study of inflammation-induced MDSCs led to the development of a novel strategy of distinguishing granulocytic MDSCs from monocytic MDSCs in septic mice by expression of CD48. Application of this novel model should help achieve a more accurate understanding of the inflammation-induced MDSC activity.

scholarly journals A new transgene mouse model using an extravesicular EGFP tag to elucidate the in vivo function of extracellular vesicles

2021 ◽  
Author(s):  
Mikkel Oernfeldt Noegaard ◽  
Lasse Bach Steffensen ◽  
Didde Hansen ◽  
Ernst-Martin Fuchtbauer ◽  
Morten Buch Engelund ◽  
...  
Keyword(s):  
Mouse Model ◽  
Extracellular Vesicles ◽  
Fluorescent Protein ◽  
Urine Samples ◽  
Egfp Expression ◽  
Reporter Mice ◽  
Plasma And Urine Samples ◽  
Co Precipitation ◽  
Green Fluorescent

The in vivo function of cell-derived extracellular vesicles (EVs) is challenging to establish since cell-specific EVs are difficult to isolate. We therefore created an EV reporter using CD9 to display enhanced green fluorescent protein (EGFP) on the EV surface. CD9-EGFP expression in cells did not affect EV size and concentration, but allowed for co-precipitation of EV markers TSG101 and ALIX from cell-conditioned medium by anti-GFP immunoprecipitation. We created a transgenic mouse where CD9-EGFP was inserted in the inverse orientation and double-floxed, ensuring Cre recombinase-dependent EV reporter expression. We crossed the EV reporter mice with mice expressing Cre ubiquitously (CMV-Cre), in cardiomyocytes (AMHC-Cre) and kidney epithelium (Pax8-Cre), respectively. The mice showed tissue-specific EGFP expression, and plasma and urine samples were used to immunoprecipitate EVs. CD9-EGFP EVs was detected in plasma samples from CMV-Cre/CD9-EGFP and AMHC-Cre/CD9-EGFP mice, but not in PAX8-Cre/CD9-EGFP mice. On the other hand, CD9-EGFP EVs were detected in urine samples from CMV-Cre/CD9-EGFP and PAX8-Cre/CD9-EGFP mice, but not AMHC-Cre/CD9-EGFP, indicating that plasma EVs are not filtered to the urine. In conclusion, our EV reporter mouse model enables Cre-dependent EV labeling, providing a new approach to study cell-specific EVs in vivo and gain new insight into their physiological and pathophysiological function.

Analysis of the Myeloid-Derived Suppressor Cells and Annexin A1 in Multibacillary Leprosy and Reactional Episodes

2020 ◽  
Author(s):  
Amilcar Sabino Damazo ◽  
Stephanni Figueiredo da Silva ◽  
Leticia Rossetto da Silva Cavalcante ◽  
Ezequiel Angelo Fonseca Junior ◽  
Joselina Maria da Silva ◽  
...  
Keyword(s):  
Suppressor Cells ◽  
Suppressor Cell ◽  
Mycobacterium Leprae ◽  
Histopathological Analysis ◽  
Annexin A1 ◽  
Myeloid Derived Suppressor Cells ◽  
Myeloid Derived Suppressor Cell ◽  
Leprosy Patients ◽  
Multibacillary Leprosy

Abstract Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Patients have distinct clinical forms, and host´s immunological response regulate those manifestations. In this work, the presence of the myeloid-derived suppressor cell and the regulatory protein annexin A1 is described in patients with multibacillary leprosy and with type 1 and 2 reactions. Methods: Patients were submitted to skin biopsy for histopathological analysis to obtain bacilloscopic index. Immunofluorescence was used to detect myeloid-derived suppressor cells and annexin A1.Results: The data demonstrated that the presence of granulocytic and monocytic myeloid-derived suppressor cells in leprosy patients. The high number of monocytic myeloid-derived suppressor cells were observed in lepromatous leprosy and type 2 reactional patients with Bacillus Calmette–Guérin (BCG) vaccination scar. The presence of annexin A1 was observed in all myeloid-derived suppressor cells. In particularly, the monocytic myeloid-derived suppressor cell in the lepromatous patients has higher levels of this protein when compared to the reactional patients. This data suggest that the higher expression of this protein may be related to regulatory response against a severe infection, contributing to anergic response. In type 1 reactional patients, the expression of annexin A1 was reduced. Conclusions: Myeloid-derived suppressor cell are present in leprosy patients and annexin A1 might be regulated the host response against Mycobacterium leprae.

scholarly journals Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis

Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
McKenzie K. Hollen ◽  
Julie A. Stortz ◽  
Dijoia Darden ◽  
Marvin L. Dirain ◽  
Dina C. Nacionales ◽  
...  
Keyword(s):  
Cell Function ◽  
Expression Patterns ◽  
Suppressor Cells ◽  
Myeloid Cell ◽  
Suppressor Cell ◽  
Myeloid Derived Suppressor Cell ◽  
T Lymphocyte Proliferation ◽  
Suppressive Phenotype ◽  
Sepsis Survivors ◽  
Over Time

Abstract Background Sepsis is an increasingly significant challenge throughout the world as one of the major causes of patient morbidity and mortality. Central to the host immunologic response to sepsis is the increase in circulating myeloid-derived suppressor cells (MDSCs), which have been demonstrated to be present and independently associated with poor long-term clinical outcomes. MDSCs are plastic cells and potentially modifiable, particularly through epigenetic interventions. The objective of this study was to determine how the suppressive phenotype of MDSCs evolves after sepsis in surgical ICU patients, as well as to identify epigenetic differences in MDSCs that may explain these changes. Methods Circulating MDSCs from 267 survivors of surgical sepsis were phenotyped at various intervals over 6 weeks, and highly enriched MDSCs from 23 of these samples were co-cultured with CD3/CD28-stimulated autologous T cells. microRNA expression from enriched MDSCs was also identified. Results We observed that MDSC numbers remain significantly elevated in hospitalized sepsis survivors for at least 6 weeks after their infection. However, only MDSCs obtained at and beyond 14 days post-sepsis significantly suppressed T lymphocyte proliferation and IL-2 production. These same MDSCs displayed unique epigenetic (miRNA) expression patterns compared to earlier time points. Conclusions We conclude that in sepsis survivors, immature myeloid cell numbers are increased but the immune suppressive function specific to MDSCs develops over time, and this is associated with a specific epigenome. These findings may explain the chronic and persistent immune suppression seen in these subjects.

Metabolic changes and interaction of tumor cell, myeloid-derived suppressor cell and T cell in hypoxic microenvironment

2020 ◽  
Author(s):  
Xiantu Ou ◽  
Weibiao Lv
Keyword(s):  
Tumor Microenvironment ◽  
Regulatory Protein ◽  
Tumor Hypoxia ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Inflammatory Factors ◽  
Tumor Escape ◽  
Myeloid Derived Suppressor Cells ◽  
Myeloid Derived Suppressor Cell ◽  
Transcriptional Regulatory

It is universally acknowledged that a large number of immune cells, as well as inflammatory factors, regulatory factors and metabolites, accumulate in the tumor microenvironment to jointly promote tumor escape, development and metastasis. Hypoxia is one of the characteristics in tumor microenvironment and is a common phenomenon in all solid tumors. In tumor hypoxia response, there is a key regulator called HIF-1a, which is a key transcriptional regulatory protein that regulates many critical genes. In this paper, the effects of hypoxia on glucose metabolism of tumor cells, myeloid-derived suppressor cells and T cells in tumor microenvironment were reviewed, and the interaction among the three was also described.

scholarly journals Myeloid-derived suppressor cell cytokine secretion as prognostic factor in myelodysplastic syndromes

2020 ◽  
Vol 26 (8) ◽  
pp. 703-715
Author(s):  
Dong Han ◽  
Jinglian Tao ◽  
Rong Fu ◽  
Zonghong Shao
Keyword(s):  
Functional Status ◽  
Myelodysplastic Syndromes ◽  
Poor Prognosis ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Biological Research ◽  
Myeloid Derived Suppressor Cell ◽  
Tnf Α ◽  
Blast Cells ◽  
Immature Myeloid Cells

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that play a critical immunosuppressive role in the tumour micro-environment. Although biological research on MDSCs has made progress, the relationship between the secretion of cytokines by MDSCs and poor prognosis is not clear, and there are no criteria to measure the functional status of MDSCs. Here, we detected the mRNA expression of IL-10, IL-12, TGF-β and TNF-α in MDSCs and the levels of these cytokines in MDSC culture supernatants of patients with myelodysplastic syndromes, and quantified the functional status of MDSCs by IL-10/IL-12 ratio and TGF-β/TNF-α ratio. We found that the ratio of IL-10/IL-12 and TGF-β/TNF-α was significantly higher in higher-risk MDS than in lower-risk MDS and normal control groups. The TGF-β/TNF-α ratio in MDSCs was positively correlated with the percentage of blast cells and was negatively correlated with the percentage of CD3+CD8+ T lymphocytes. Meanwhile, the TGF-β/TNF-α ratio was higher in patients with a lower absolute neutrophil count. It suggested that MDSCs in higher-risk MDS have a stronger immunosuppressive effect and might be related to poor prognosis. Quantifying the functional status of MDSCs with IL-10/IL-12 and TGF-β/TNF-α ratio might help to evaluate the balance of cellular immunity of MDSCs in MDS.

scholarly journals Cholangiocarcinoma presents a distinct myeloid-derived suppressor cell signature compared to other hepatobiliary cancers

2019 ◽  
Author(s):  
Defne Bayik ◽  
Adam J. Lauko ◽  
Gustavo A. Roversi ◽  
Emily Serbinowski ◽  
Lou-Anne Acevedo-Moreno ◽  
...  
Keyword(s):  
Suppressor Cells ◽  
Myeloid Cell ◽  
Suppressor Cell ◽  
The Cancer Genome Atlas ◽  
Limiting Factor ◽  
Isocitrate Dehydrogenase 1 ◽  
Myeloid Derived Suppressor Cell ◽  
Liver Cancers ◽  
Malignant Liver ◽  
Immunosuppressive Cells

AbstractMyeloid-derived suppressor cells (MDSCs) are immunosuppressive cells that are increased in patients with numerous malignancies including viral-derived hepatocellular carcinoma (HCC). Here, we report an elevation of MDSC in other hepatobiliary malignancies including non-viral HCC, neuroendocrine tumors (NET), colorectal carcinoma with liver metastases (CRLM), but not cholangiocarcinoma (CCA). Investigation of myeloid cell infiltration in HCC, NET and intrahepatic CCA tumors further established that the frequency of antigen-presenting cells was limited compared to benign lesions suggesting that primary and metastatic hepatobiliary cancers have distinct peripheral and tumoral myeloid signatures. Bioinformatics analysis of the Cancer Genome Atlas demonstrated that a high MDSC score in HCC patients predicted poor disease outcome. Mechanistic studies indicated that the oncometabolite D-2-hydroxyglutarate resulting from isocitrate dehydrogenase 1 mutation could be a limiting factor of MDSC accumulation in CCA patients. Given our observation that MDSCs are increased in non-CCA malignant liver cancers, they may comprise suitable targets for effective immunotherapy approaches.

scholarly journals Myeloid-Derived Suppressor Cells: A Multifaceted Accomplice in Tumor Progression

2021 ◽  
Vol 9 ◽  
Author(s):  
Jia-Nan Cheng ◽  
Yi-Xiao Yuan ◽  
Bo Zhu ◽  
Qingzhu Jia
Keyword(s):  
T Cells ◽  
Tumor Progression ◽  
Therapeutic Response ◽  
Cytotoxic T Cells ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Myeloid Derived Suppressor Cell ◽  
Immunosuppressive Tumor Microenvironment ◽  
Immature Myeloid Cells ◽  
Underlying Mechanisms

Myeloid-derived suppressor cell (MDSC) is a heterogeneous population of immature myeloid cells, has a pivotal role in negatively regulating immune response, promoting tumor progression, creating pre-metastases niche, and weakening immunotherapy efficacy. The underlying mechanisms are complex and diverse, including immunosuppressive functions (such as inhibition of cytotoxic T cells and recruitment of regulatory T cells) and non-immunological functions (mediating stemness and promoting angiogenesis). Moreover, MDSC may predict therapeutic response as a poor prognosis biomarker among multiple tumors. Accumulating evidence indicates targeting MDSC can reverse immunosuppressive tumor microenvironment, and improve therapeutic response either single or combination with immunotherapy. This review summarizes the phenotype and definite mechanisms of MDSCs in tumor progression, and provide new insights of targeting strategies regarding to their clinical applications.

scholarly journals Analysis of the myeloid-derived suppressor cells and annexin A1 in multibacillary leprosy and reactional episodes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stephanni Figueiredo da Silva ◽  
Leticia Rossetto da Silva Cavalcante ◽  
Ezequiel Angelo Fonseca Junior ◽  
Joselina Maria da Silva ◽  
José Cabral Lopes ◽  
...  
Keyword(s):  
Suppressor Cells ◽  
Suppressor Cell ◽  
Mycobacterium Leprae ◽  
Histopathological Analysis ◽  
Annexin A1 ◽  
Myeloid Derived Suppressor Cells ◽  
Myeloid Derived Suppressor Cell ◽  
Leprosy Patients ◽  
Multibacillary Leprosy

Abstract Background Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Patients have distinct clinical forms, and the host´s immunological response regulate those manifestations. In this work, the presence of the myeloid-derived suppressor cell and the regulatory protein annexin A1 is described in patients with multibacillary leprosy and with type 1 and 2 reactions. Methods Patients were submitted to skin biopsy for histopathological analysis to obtain a bacilloscopic index. Immunofluorescence was used to detect myeloid-derived suppressor cells and annexin A1. Results The data demonstrated that the presence of granulocytic and monocytic myeloid-derived suppressor cells in leprosy patients. A high number of monocytic myeloid-derived suppressor cells were observed in lepromatous leprosy and type 2 reactional patients. The presence of annexin A1 was observed in all myeloid-derived suppressor cells. In particular, the monocytic myeloid-derived suppressor cell in the lepromatous patients has higher levels of this protein when compared to the reactional patients. This data suggest that the higher expression of this protein may be related to regulatory response against a severe infection, contributing to anergic response. In type 1 reactional patients, the expression of annexin A1 was reduced. Conclusions Myeloid-derived suppressor cell are present in leprosy patients and annexin A1 might be regulated the host response against Mycobacterium leprae.

scholarly journals Hepatobiliary malignancies have distinct peripheral myeloid-derived suppressor cell signatures and tumor myeloid cell profiles

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Defne Bayik ◽  
Adam J. Lauko ◽  
Gustavo A. Roversi ◽  
Emily Serbinowski ◽  
Lou-Anne Acevedo-Moreno ◽  
...  
Keyword(s):  
Suppressor Cells ◽  
Myeloid Cell ◽  
Suppressor Cell ◽  
The Cancer Genome Atlas ◽  
Hepatobiliary Malignancies ◽  
Myeloid Derived Suppressor Cell ◽  
Liver Cancers ◽  
Malignant Liver ◽  
Immunosuppressive Cells ◽  
Antigen Presenting

Abstract Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells that are increased in patients with numerous malignancies including viral-derived hepatocellular carcinoma (HCC). Here, we report an elevation of MDSCs in the peripheral blood of patients with other hepatobiliary malignancies including non-viral HCC, neuroendocrine tumors (NET), and colorectal carcinoma with liver metastases (CRLM), but not cholangiocarcinoma (CCA). The investigation of myeloid cell infiltration in HCC, NET and intrahepatic CCA tumors further established that the frequency of antigen-presenting cells was limited compared to benign lesions, suggesting that primary and metastatic hepatobiliary cancers have distinct peripheral and tumoral myeloid signatures. Bioinformatics analysis of The Cancer Genome Atlas dataset demonstrated that a high MDSC score in HCC patients is associated with poor disease outcome. Given our observation that MDSCs are increased in non-CCA malignant liver cancers, these cells may represent suitable targets for effective immunotherapy approaches.

Sign in / Sign up

Export Citation Format

Share Document