scholarly journals Mechanisms of immune suppression by myeloid-derived suppressor cells: the role of interleukin-10 as a key immunoregulatory cytokine

Open Biology ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 200111 ◽  
Author(s):  
Mahmoud Mohammad Yaseen ◽  
Nizar Mohammad Abuharfeil ◽  
Homa Darmani ◽  
Ammar Daoud
Keyword(s):  
Immune Responses ◽  
Disease Progression ◽  
Immune Activation ◽  
Pathological Condition ◽  
Suppressor Cells ◽  
Interleukin 10 ◽  
Myeloid Derived Suppressor Cells ◽  
Chronic Infections ◽  
Pathological Conditions

Chronic immune activation and inflammation are unwanted consequences of many pathological conditions, since they could lead to tissue damage and immune exhaustion, both of which can worsen the pathological condition status. In fact, the immune system is naturally equipped with immunoregulatory cells that can limit immune activation and inflammation. However, chronic activation of downregulatory immune responses is also associated with unwanted consequences that, in turn, could lead to disease progression as seen in the case of cancer and chronic infections. Myeloid-derived suppressor cells (MDSCs) are now considered to play a pivotal role in the pathogenesis of different inflammatory pathological conditions, including different types of cancer and chronic infections. As a potent immunosuppressor cell population, MDSCs can inhibit specific and non-specific immune responses via different mechanisms that, in turn, lead to disease persistence. One such mechanism by which MDSCs can activate their immunosuppressive effects is accomplished by secreting copious amounts of immunosuppressant molecules such as interleukin-10 (IL-10). In this article, we will focus on the pathological role of MDSC expansion in chronic inflammatory conditions including cancer, sepsis/infection, autoimmunity, asthma and ageing, as well as some of the mechanisms by which MDSCs/IL-10 contribute to the disease progression in such conditions.

Abstract 543: Regulation of Atherosclerosis by Myeloid-Derived Suppressor Cells

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Amanda C Foks ◽  
Gijs H van Puijvelde ◽  
Vanessa Frodermann ◽  
Thomas van der Heiden ◽  
Ilze Bot ◽  
...  
Keyword(s):  
Immune Responses ◽  
Magnetic Beads ◽  
Immune Therapy ◽  
Atherosclerotic Lesion ◽  
Suppressor Cells ◽  
Lymphoid Tissues ◽  
Dependent Manner ◽  
Myeloid Derived Suppressor Cells ◽  
Immature Myeloid Cells

Objective: Restoration of immune homeostasis in atherosclerosis represents the ultimate goal of an immune-based therapy. Myeloid-derived suppressor cells (MDSCs) are a population of immature myeloid cells that potently suppress immune responses in various pathological settings, via multiple mechanisms, including inhibition of T cell responses. They express the myeloid markers CD11b and Gr-1 and can accumulate in various lymphoid and non-lymphoid tissues. In the present study, we determined the role of MDSCs in atherosclerosis by an adoptive transfer of CD11b + Gr-1 + cells into LDLr -/- mice fed a Western-type diet. Methods and Results: We isolated CD11b + Gr-1 + cells from the bone marrow of LDLr -/- mice fed a Western-type diet for 2 weeks with magnetic beads and found that they strongly suppressed αCD3/CD28-induced splenocyte proliferation in an IFN-γ and iNOS-dependent manner. Subsequently, we adoptively transferred MDSCs into LDLr -/- mice fed a Western-type diet for 6 weeks, which resulted in a 35% reduction in atherosclerotic lesion formation in the aortic root. MDSC treatment reduced splenic Th1 and Th17 cells with 50% and diminished B cells, in particular circulating B2 cells, and concomitantly impaired their proliferative capacity. Conclusions: Our data prove that MDSCs could represent a novel cell-based immune-therapy to dampen pro-atherogenic immune responses and thereby reduce atherosclerosis.

scholarly journals Myeloid-Derived Suppressor Cells Participate in Preventing Graft Rejection

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Yan Wang ◽  
Xiaodong Gu ◽  
Jianbin Xiang ◽  
Zongyou Chen
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Suppressor Cells ◽  
Heterogeneous Population ◽  
Myeloid Derived Suppressor Cells ◽  
Transplant Tolerance ◽  
Pathological Conditions ◽  
T Cell Immune Responses

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells and have a tremendous potential to suppress immune responses. MDSCs accumulate during tumor progression, autoimmunity, chronic infection, transplantation, and other pathological conditions and can potently suppress T-cell function. Here, we discuss recent findings that describe the molecular mechanisms of MDSCs suppressing T-cell immune responses as well as recent observations that MDSCs may have roles in transplant tolerance.

scholarly journals Interleukin-10 Produced by Myeloid-Derived Suppressor Cells Provides Protection to Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 258 by Enhancing Its Clearance in the Airways

2019 ◽  
Vol 87 (5) ◽  
Author(s):  
Hernán F. Peñaloza ◽  
Loreani P. Noguera ◽  
Danielle Ahn ◽  
Omar P. Vallejos ◽  
Raquel M. Castellanos ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Suppressor Cells ◽  
Interleukin 10 ◽  
Sequence Type ◽  
Lung Damage ◽  
Myeloid Derived Suppressor Cells ◽  
Chronic Infections ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Time Of Infection

ABSTRACT Carbapenem-resistant Klebsiella pneumoniae sequence type 258 (CRKP-ST258) can cause chronic infections in lungs and airways, with repeated episodes of bacteremia. In this report we addressed whether the recruitment of myeloid cells producing the anti-inflammatory cytokine interleukin-10 (IL-10) modulates the clearance of CKRP-ST258 in the lungs and establishes bacterial persistence. Our data demonstrate that during pneumonia caused by a clinical isolate of CRKP-ST258 (KP35) there is an early recruitment of monocyte-myeloid-derived suppressor cells (M-MDSCs) and neutrophils that actively produce IL-10. However, M-MDSCs were the cells that sustained the production of IL-10 over the time of infection evaluated. Using mice unable to produce IL-10 (IL-10−/−), we observed that the production of this cytokine during the infection caused by KP35 is important to control bacterial burden, to prevent lung damage, to modulate cytokine production, and to improve host survival. Importantly, intranasal transfer of bone marrow-derived M-MDSCs from mice able to produce IL-10 at 1 day prior to infection improved the ability of IL-10−/− mice to clear KP35 in the lungs, decreasing their mortality. Altogether, our data demonstrate that IL-10 produced by M-MDSCs is required for bacterial clearance, reduction of lung tissue damage, and host survival during KP35 pneumonia.

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