scholarly journals Increased Levels of Granulocytic Myeloid-Derived Suppressor Cells in Peripheral Blood and Tumour Tissue of Pancreatic Cancer Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yazan S. Khaled ◽  
Basil J. Ammori ◽  
Eyad Elkord
Keyword(s):  
Pancreatic Cancer ◽  
Suppressor Cells ◽  
Blood Levels ◽  
Myeloid Derived Suppressor Cells ◽  
Arginase 1 ◽  
Hla Dr ◽  
Healthy Donors ◽  
And Function ◽  
Immunosuppressive Cells

Pancreatic cancer (PC) often presents late with poor survival. While role of immunosuppressive cells in preclinical studies provided help to develop immunotherapeutic agents, these cells remain under investigation in PC. The aim of this study was to characterise the different subsets of myeloid-derived suppressor cells (MDSCs) and evaluate their level and function in the circulation and tissue of PC patients. Significant increases in circulating and tumour-infiltrating granulocytic (Lin-HLA-DR-CD33+CD11b+CD15+), but not monocytic (Lin-HLA-DR-CD14+), MDSCs were detected in PC patients when compared with healthy donors and patients with chronic pancreatitis. The circulating MDSCs from PC patients expressed arginase 1, which represents their functional state. Blood levels of MDSCs showed no association with PC stage or preoperative levels of tumour markers. These findings provide a first characterisation of the phenotype of different subsets of peripheral and local MDSCs in PC patients and suggest that the frequency and contribution of these cells are predominantly granulocytic. This information demonstrates that MDSCs play a role in pancreatic cancer and future large validation studies may help in the development of new immunotherapeutic strategies to inhibit or eliminate MDSC function.

scholarly journals Expansion of Myeloid-Derived Suppressor Cells in Patients with Acute Coronary Syndrome

2015 ◽  
Vol 35 (1) ◽  
pp. 292-304 ◽  
Author(s):  
Yan-ge Wang ◽  
Xin Xiong ◽  
Zhu-yue Chen ◽  
Kan-ling Liu ◽  
Jin-hua Yang ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Plasma Levels ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Suppressive Function ◽  
Coronary Syndrome ◽  
Arginase 1 ◽  
Hla Dr ◽  
Tnf Α ◽  
And Function

Aim: The aim of this study was to explore whether the circulating frequency and function of myeloid-derived suppressor cells (MDSCs) are altered in patients with acute coronary syndrome (ACS). Methods: The frequency of MDSCs in peripheral blood was determined by flow cytometry, and mRNA expression in purified MDSCs was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). The suppressive function of MDSCs isolated from different groups was also determined. The plasma levels of certain cytokines were determined using Bio-Plex Pro™ Human Cytokine Assays. Results: The frequency of circulating CD14+HLA-DR-/low MDSCs; arginase-1 (Arg-1) expression; and plasma levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-33 were markedly increased in ACS patients compared to stable angina (SA) or control patients. Furthermore, MDSCs from ACS patients were more potent suppressors of T-cell proliferation and IFN-γ production than those from the SA or control groups at ratios of 1:4 and 1:2; this effect was partially mediated by Arg-1. In addition, the frequency of MDSCs was positively correlated with plasma levels of IL-6, IL-33, and TNF-α. Conclusions: We observed an increased frequency and suppressive function of MDSCs in ACS patients, a result that may provide insights into the mechanisms involved in ACS.

Dendritic Cell Vaccination in Acute Leukemia Patients Induces Reduction of Myeloid-Derived Suppressor Cells : Immunological Analysis of a Pilot Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1113-1113 ◽  
Author(s):  
Masahiro Ogasawara ◽  
Shuichi Ota
Keyword(s):  
T Cells ◽  
Acute Leukemia ◽  
Suppressor Cells ◽  
Absolute Number ◽  
The Other ◽  
Myeloid Derived Suppressor Cells ◽  
Arginase 1 ◽  
Hla Dr ◽  
Healthy Donors ◽  
Before And After

Abstract Background and Purpose: Myeloid-derived suppressor cells (MDSC) are a heterogeneous cell population that have an immunesuppresive function and play an important role in tumor immunology and self tolerance. Elevated levels of MDSCs in peripheral blood (PB) are reported in various cancers and hematological malignancies such as MDS, NHL and MM. We reported that vaccination with Wilms’ tumor 1 (WT1) peptide-pulsed dendritic cells (DC) in NHL patients induced not only WT1 specific immune responses but also innate immunity which correlated with clinical efficacy (ASH 2013). In the present study, we focused on MDSCs and investigated the effects of DC vaccination on the alteration of MDSCs which have negative influence on disease progression. Patients and Methods: 8 patients with acute leukemia (6 AML and 2ALL patients; aged 16-77) who were treated with WT1 peptide-loaded DC vaccination were enrolled in the present study. MDSCs were analyzed by FACS. Linage negative, CD11b+CD33+HLA-DR- cells were defined as MDSC. Monocytic and granulocytic MDSC were defined as CD14+HLA-DRlow/- and CD15+CD11b+CD33+HLA-DR-, respectively. For proliferation assay, CD14+DR- cells and CD3+ T cells were isolated by magnetic beads method. CFSE-labeled CD3+ T cells were stimulated with anti-CD3 and anti-CD28 moAb together with IL-2 in the presence or absence of CD14+DR-cells for 4 days and cell division was analyzed by FACS. Cytoplasmic staining of indoleamine 2,3-deoxygenase (IDO) and arginase 1 were performed by permeabilization using saponin followed by moAb staining. Arginase 1 protein levels in plasma was assessed using a commercially available ELISA kit. Results: 3 patients were in complete remission (responder) and 5 others were in disease progression (non-responder) following one course of vaccination. WT1 specific T cell responses evaluated by a HLA-tetramer assay and a delayed type hypersensitivity (DTH) test were observed in all the responders and 2 non-responders. Mean percentage of MDSCs, monocytic and granulocytic MDSCs in PB was higher in acute leukemia patients than in healthy donors (1.60±0.72%, 16.56±6.07%, 1.34±0.69%, respectively in patients; 0.60±0.31%, 13.1±4.1%, 0.37±0.1%, respectively in healthy donors). Absolute number of circulating monocytic and granulocytic MDSCs before and after vaccination in responders was 359.4±117.8/μl and 35.2±14.8/μl, 282.8±119.2 /μl and 14.4±12.0/μl, respectively. On the other hand, those in non-responders were 126.3±60.2/μl and 36.3±21.7/μl, 181.3±124.0/μl and 65.1±12.0/μl, respectively. While DC vaccination resulted in reduction of both monocytic and granulocytic MDSCs by 21.3% and 59.1%, respectively in responders, it induced augmentation of these MDSCs by 43.5% and 79.3%, respectively in non-responders. A portion of MDSCs expressed IDO and arginase 1 in cytoplasm. While the percentage of IDO positive cells in monocytic MDSCs increased by 2.2 and 2.3 times in responders and non-responders, respectively following vaccination, the positivity of arginase 1 decreased by 59% in responders. On the other hand, the positivity of IDO and arginase 1 in granulocytic MDSCs decreased at the same level in both responders and non-responders following vaccination. CD14+DR-cells inhibited the proliferation of CD3+ T cells in a dose dependent manner, indicating that these cells share characteristics of MDSCs. The inhibition of the proliferation of CD3+T cells was partially restored by the addition of 1-methyl-DL-tryptophan (IDO inhibitor) and Nω-hydroxy-nor-arginine (arginase 1 inhibitor), suggesting that the inhibition was mediated at least in part by IDO and arginase 1. Amount of arginase 1 in the plasma before and after vaccination decreased by 25% in responders, not in non-responders. Conclusions: These results demonstrated that DC vaccination resulted in the reduction of the absolute number of MDSCs which seems to be correlated with clinical efficacy. DC vaccination may have inhibitory effects on several functions of MDSCs that can suppress immune surveillance against leukemia, which is favorable for regression of leukemia cells. Disclosures No relevant conflicts of interest to declare.

scholarly journals Energy metabolism manipulates the fate and function of tumour myeloid-derived suppressor cells

2019 ◽  
Vol 122 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Cong Hu ◽  
Bo Pang ◽  
Guangzhu Lin ◽  
Yu Zhen ◽  
Huanfa Yi
Keyword(s):  
Metabolic Pathways ◽  
Immune Surveillance ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Metabolic Energy ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Responses ◽  
And Function ◽  
Promote Tumour Development

AbstractIn recent years, a large number of studies have been carried out in the field of immune metabolism, highlighting the role of metabolic energy reprogramming in altering the function of immune cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells generated during a large array of pathological conditions, such as cancer, inflammation, and infection, and show remarkable ability to suppress T-cell responses. These cells can also change their metabolic pathways in response to various pathogen-derived or inflammatory signals. In this review, we focus on the roles of glucose, fatty acid (FA), and amino acid (AA) metabolism in the differentiation and function of MDSCs in the tumour microenvironment, highlighting their potential as targets to inhibit tumour growth and enhance tumour immune surveillance by the host. We further highlight the remaining gaps in knowledge concerning the mechanisms determining the plasticity of MDSCs in different environments and their specific responses in the tumour environment. Therefore, this review should motivate further research in the field of metabolomics to identify the metabolic pathways driving the enhancement of MDSCs in order to effectively target their ability to promote tumour development and progression.

scholarly journals Analysis of Monocytic and Granulocytic Myeloid-Derived Suppressor Cells Subsets in Patients with Hepatitis C Virus Infection and Their Clinical Significance

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Gang Ning ◽  
Lanhui She ◽  
Lirong Lu ◽  
Ying Liu ◽  
Yingfu Zeng ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Clinical Significance ◽  
Suppressor Cells ◽  
Hcv Rna ◽  
Myeloid Derived Suppressor Cells ◽  
Hepatitis C Virus Infection ◽  
Cell Responses ◽  
Hla Dr ◽  
Healthy Donors

Myeloid-derived suppressor cells (MDSCs) have been shown to inhibit T-cell responses in many diseases, but, in hepatitis C virus (HCV) infected patients, MDSCs are still poorly studied. In this assay, we investigated the phenotype and frequency of two new populations of MDSCs denoted as monocytic and granulocytic MDSCs (M-MDSCs and G-MDSCs) in HCV infected patients and analyzed their clinical significance in these patients respectively. We found that the frequency of CD14+HLA-DR-/lowcells (M-MDSCs) from HCV infected patients (mean ± SE, 3.134% ± 0.340%) was significantly increased when compared to healthy controls (mean ± SE, 1.764% ± 0.461%) (Z= −2.438,P= 0.015), while there was no statistical difference between the frequency ofHLA-DR-/lowCD33+CD11b+CD15+(G-MDSCs) of HCV infected patients and healthy donors (0.201% ± 0.038% versus 0.096% ± 0.026%,P> 0.05), which suggested that HCV infection could cause the proliferation of M-MDSCs instead of G-MDSCs. Besides, we found that the frequency of M-MDSCs in HCV infected patients had certain relevance with age (r= 0.358,P= 0.003); patients older than 40 years old group (mean ± SE, 3.673% ± 0.456%) had a significantly higher frequency of M-MDSCs than that of age less than 40 years old group (mean ± SE, 2.363% ± 0.482%) (Z= −2.685,P= 0.007). The frequency of M-MDSCs, however, had no correlation with HCV RNA loads, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the level of liver inflammation degree.

scholarly journals Stroke-Induced Modulation of Myeloid-Derived Suppressor Cells (MDSCs) and IL-10-Producing Regulatory Monocytes

2020 ◽  
Vol 11 ◽  
Author(s):  
Lennart Achmus ◽  
Johanna Ruhnau ◽  
Sascha Grothe ◽  
Bettina von Sarnowski ◽  
Barbara M. Bröker ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Geometric Mean ◽  
Suppressor Cells ◽  
Interleukin 10 ◽  
Experimental Stroke ◽  
Myeloid Derived Suppressor Cells ◽  
Stroke Patients ◽  
Post Stroke ◽  
Arginase 1 ◽  
Hla Dr

Background: Stroke patients are at risk of acquiring secondary infections due to stroke-induced immune suppression (SIIS). Immunosuppressive cells comprise myeloid-derived suppressor cells (MDSCs) and immunosuppressive interleukin 10 (IL-10)-producing monocytes. MDSCs represent a small but heterogeneous population of monocytic, polymorphonuclear (or granulocytic), and early progenitor cells (“early” MDSC), which can expand extensively in pathophysiological conditions. MDSCs have been shown to exert strong immune-suppressive effects. The role of IL-10-producing immunosuppressive monocytes after stroke has not been investigated, but monocytes are impaired in oxidative burst and downregulate human leukocyte antigen—DR isotype (HLA-DR) on the cell surface.Objectives: The objective of this work was to investigate the regulation and function of MDSCs as well as the immunosuppressive IL-10-producing monocytes in experimental and human stroke.Methods: This longitudinal, monocentric, non-interventional prospective explorative study used multicolor flow cytometry to identify MDSC subpopulations and IL-10 expression in monocytes in the peripheral blood of 19 healthy controls and 27 patients on days 1, 3, and 5 post-stroke. Quantification of intracellular STAT3p and Arginase-1 by geometric mean fluorescence intensity was used to assess the functionality of MDSCs. In experimental stroke induced by electrocoagulation in middle-aged mice, monocytic (CD11b+Ly6G−Ly6Chigh) and polymorphonuclear (CD11b+Ly6G+Ly6Clow) MDSCs in the spleen were analyzed by flow cytometry.Results: Compared to the controls, stroke patients showed a relative increase in monocytic MDSCs (percentage of CD11b+ cells) in whole blood without evidence for an altered function. The other MDSC subgroups did not differ from the control. Also, in experimental stroke, monocytic, and in addition, polymorphonuclear MDSCs were increased. The numbers of IL-10-positive monocytes did not differ between the patients and controls. However, we provide a new insight into monocytic function post-stroke since we can report that a differential regulation of HLA-DR and PD-L1 was found depending on the IL-10 production of monocytes. IL-10-positive monocytes are more activated post-stroke, as indicated by their increased HLA-DR expression.Conclusions: MDSC and IL-10+ monocytes can induce immunosuppression within days after stroke.

Increased Frequencies Of Myeloid-Derived Suppressor Cells and Regulatory T-Cells Decrease Response To Donor Lymphocyte Infusions, Independent Of Graft Versus Host Disease In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2005-2005
Author(s):  
Laurens E. Franssen ◽  
Maarten E. Emmelot ◽  
Niels W.C.J. van de Donk ◽  
Henk Lokhorst ◽  
Tuna Mutis
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Research Funding ◽  
Suppressor Cells ◽  
Cellular Immunotherapy ◽  
Myeloid Derived Suppressor Cells ◽  
Graft Versus Host ◽  
Hla Dr ◽  
Healthy Donors ◽  
Donor Lymphocyte Infusions

Abstract Background Allogeneic stem cell transplantation (allo-SCT) followed by donor lymphocyte infusions (DLI) can induce durable responses in multiple myeloma (MM) by virtue of the graft versus myeloma (GvM) effect. However, this is only true for a minority of patients and relapse rates after reaching an initial remission remain high. Also, transplant-related mortality and Graft-versus-Host-Disease (GvHD) are still major complications. Towards improving cellular immunotherapy we set out to identify the immune cell subsets that are involved in the GvM effect and GvHD. Myeloid-Derived Suppressor Cells (MDSCs) are a heterogeneous population of bone marrow-derived myeloid cells, with strong immunosuppressive capacity. In general, they are divided into monocyte-like M-MDSCs en granulocyte-like G-MDSCs. In myeloma, they have been shown to be present in increased frequencies, inhibit T-cell proliferation and promote multiple myeloma cell growth in vitro. Furthermore, regulatory T-cells (T-regs) seem to suppress cellular anti-tumor responses in MM. Methods To determine whether MDSCs and T-regs hamper immunotherapy, we investigated MDSCs and T-regs in peripheral blood (PB) (n=43) from post-allo SCT MM patients, prior to their first DLI, and from healthy donors (n=13). All patients had persistent or progressive disease after allo-SCT. DLI dose was 107 T-cells/kg for sibling donors (n=20) and 106 T-cells/kg for matched unrelated donors (n=23). Results We observed a significantly higher frequency of M-MDSCs (CD14+ HLA-DR-/low) (mean 5.7 vs. 0.7%, P<0.001) and T-regs (CD4+ CD25+ CD127-/low) (11.4 vs. 5.5%, P<0.01), but not of G-MDSCs (CD11b+ HLA-DR-/low CD14-CD33+) in PB of MM patients versus healthy donors. Interestingly, patients responding to DLI had significantly lower amounts of immunosuppressive G-MDSCs (mean 0.6 vs. 1.2%, P=0.04) and T-regs (7.9 vs. 13.9%, P=0.02) in their PB prior to DLI. There was no difference in M-MDSCs between responding and non-responding patients. This effect on GvM was independent of GvHD, as levels of G-MDSCs, M-MDSCs and T-regs did not differ between GvHD+ and GvHD-groups. Conclusion We show that increased frequencies of G-MDSCs and T-regs are associated with resistance to DLI, independent of the occurrence of GvHD. Our data suggest that targeting G-MDSCs as well as T-regs may improve cellular immunotherapy in multiple myeloma. Disclosures: van de Donk: Celgene: Research Funding. Lokhorst:Genmab A/S: Consultancy, Research Funding; Celgene: Honoraria; Johnson-Cilag: Honoraria; Mudipharma: Honoraria.

scholarly journals The Consequence of Immune Suppressive Cells in the Use of Therapeutic Cancer Vaccines and Their Importance in Immune Monitoring

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Matteo Vergati ◽  
Jeffrey Schlom ◽  
Kwong Y. Tsang
Keyword(s):  
Cancer Vaccines ◽  
T Regulatory Cells ◽  
Suppressor Cells ◽  
Immune Monitoring ◽  
Regulatory Cells ◽  
Phenotypic Characteristics ◽  
And Function ◽  
Immunosuppressive Cells ◽  
Therapeutic Cancer Vaccines

Evaluating the number, phenotypic characteristics, and function of immunosuppressive cells in the tumor microenvironment and peripheral blood could elucidate the antitumor immune response and provide information to evaluate the efficacy of cancer vaccines. Further studies are needed to evaluate the correlation between changes in immunosuppressive cells and clinical outcomes of patients in cancer vaccine clinical trials. This paper focuses on the role of T-regulatory cells, myeloid-derived suppressor cells, and tumor-associated macrophages in cancer and cancer immunotherapy and their role in immune monitoring.

scholarly journals Myeloid-Derived Suppressor Cells (HLA-DR-/lowCD16-CD33+) Expanded By Granulocyte Colony-Stimulating Factor Can Prevent Acute Graft-Versus-Host Disease in Humanized Mouse and Patients Following HSCT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 72-72
Author(s):  
Ke Wang ◽  
Meng Lv ◽  
Ying-Jun Chang ◽  
Xiang-Yu Zhao ◽  
Xiao-Su Zhao ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Graft Versus Host ◽  
Hla Dr ◽  
Healthy Donors

Abstract Introduction Myeloid-derived suppressor cells (MDSCs) are proposed to control graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the definition of human MDSCs has not yet reached consensus. Granulocyte colony-stimulating factor (G-CSF) has been routinely used to mobilize stem cells to peripheral blood in healthy donors. It was also recognized as a novel mediator of T-cell tolerance. However, the effects of G-CSF administration on donor-derived MDSCs and the further regulatory effects of these MDSCs on GVHD remained unclear. Amis The aim of this study is to evaluate the in vitro and in vivo effects of G-CSF expanded, donor-derived MDSCs (HLA-DR-/lowCD16-CD33+) in preventing acute GVHD after allo-HSCT. Methods The frequency and cell numbers of different kinds of MDSCs in peripheral blood before and after G-CSF administration from 10 healthy donors were analyzed by flow cytometry. Cells morphological features were detected by May-Grünwald-Giemsa cytospin. Secondly, the suppressive and regulatory functions of HLA-DR-/lowCD16-CD33+ population on CD3+ T cells were assessed via in vitro experiments. A humanized xenogeneic acute GVHD model was established to determine whether this population could prevent acute GVHD in vivo. Furthermore, a clinical prospective cohort study enrolled one hundred consecutive transplant recipients was performed to assess the effects of HLA-DR-/lowCD16-CD33+ contained in HSC grafts on the occurrence of acute GVHD. Results The findings of this study include: First, a novel phenotype of HLA-DR-/lowCD16-CD33+ MDSCs with suppressive function and morphological features similar to those of immature monocyte was identified. The median of percentages of this subset were significantly increased both in peripheral blood (PB, 6.5% vs. 4.6%, P=0.0122) and peripheral blood stem cells harvest (PBSCs, 15.5% vs. 4.6%, P<0.0001) after treating healthy donors with G-CSF than those of PB before mobilization. The median of percentage of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β) positive cells among HLA-DR-/lowCD16-CD33+ population were both significantly higher than those of PB before mobilization. (IL-10+, 10.1% vs.0.62%, P=0.002; TGF-β+, 60.24% vs. 10.39%, P=0.0003). Donor-derived HLA-DR-/lowCD16-CD33+population inhibited the proliferation of T cells in a TGF-β-dependent manner. In vitro cell co-culture experiments also showed that this MDSCs subset could promote regulatory T cells (Treg, CD4+CD25+Foxp3+) expansion and induce T helper 2(Th2, CD4+IL-4+) differentiation (The median of percentage of Treg in co-culture with MDSCs group, 21.4% vs. without MSDCs group, 8.35%, P=0.0048. The median of fold change of Th2/Th1 in co-culture with MDSCs group, 1.35 vs. without MSDCs group 0.98, P=0.0159. The median of fold change of Th2/(Th1+Th17) in co-culture with MDSCs group, 1.28 vs. without MSDCs group 1.00, P=0.0095. Th1 (CD4+IFNγ+), Th17 (CD4+IL-17A+)). Second, we demonstrated that these cells could prevent acute GVHD in a humanized mouse model. Adoptive transfer human G-CSF-mobilized HLA-DR-/lowCD16-CD33+ cells significantly prolonged the survival and ameliorated the weight loss and tissue damage in GVHD mice. Third, clinical cohort results showed that the number of HLA-DR-/lowCD33+CD16- cells in the donor graft was the only independent risk factor inversely correlated with the incidence II-IV acute GVHD in recipients (HR 0.388, 95% CI: 0.158-0.954, P=0.039). Conclusion Our results suggest that MSDCs with HLA-DR-/lowCD16-CD33+ phenotype in G-CSF-mobilized PBSCs have monocytic features and immune-regulatory properties, which could alleviate acute GVHD in the allo-HSCT settings. Key words: Myeloid-derived suppressor cells; granulocyte colony-stimulating factor; graft-versus-host disease Figure Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Myeloid - derived suppressor cells in Type 1 diabetes are an expanded population exhibiting diverse T-cell suppressor mechanisms

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242092
Author(s):  
Anna Grohová ◽  
Klára Dáňová ◽  
Irena Adkins ◽  
Zdeněk Šumník ◽  
Lenka Petruželková ◽  
...  
Keyword(s):  
At Risk ◽  
T Cells ◽  
Type 1 Diabetes ◽  
Autoimmune Diseases ◽  
Suppressor Cells ◽  
Cell Contact ◽  
Myeloid Derived Suppressor Cells ◽  
Healthy Donors

Myeloid-derived suppressor cells (MDSC) represent a heterogeneous group of immature myeloid cells with immunoregulatory function in cancer and autoimmune diseases. In humans, two subsets of MDSC were determined based on the characteristic surface markers, monocytic MDSC (M-MDSC) and granulocytic MDSC (G-MDSC). Expansion of MDSC has been reported in some murine models and patients with autoimmune diseases and their immune-suppressive properties were characterized. However, the exact role of MDSC in the pathogenesis of autoimmune diseases is more complex and/or controversial. In type 1 diabetes mellitus (T1D), the increased frequency of MDSC was found in the blood of T1D patients but their suppressor capacity was diminished. In our study, we assessed the role of M-MDSC in the pathogenesis of T1D and showed for the first time the increased frequency of M-MDSC not only in the blood of T1D patients but also in their at-risk relatives compared to healthy donors. T1D patients with inadequate long term metabolic control showed an elevation of M-MDSC compared to patients with better disease control. Furthermore, we described the positive correlation between the percentage of M-MDSC and Th17 cells and IFN-γ producing T cells in T1D patients and their at-risk relatives. Finally, we found that the ability of M-MDSC to suppress autologous T cells is efficient only at the high MDSC: T cells ratio and dependent on cell-cell-contact and TGF-β production. Our data show that the engagement of MDSC in the pathogenesis of T1D is evident, yet not entirely explored and more experiments are required to clarify whether MDSC are beneficial or harmful in T1D.

Sign in / Sign up

Export Citation Format

Share Document