The role of myeloid-derived suppressor cells (MDSC) in the inflammaging process

Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

doi:10.1016/j.arr.2018.09.001

Cited by 83 publications

(56 citation statements)

References 174 publications

(209 reference statements)

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“…The pathological switch of immature bone marrow cells to tolerogenic MDSCs is driven by tumor-derived molecules as well as epigenetic regulation [ 244 ]. MDSCs are heterogeneous populations composed of pathologically activated immature myeloid cells, which inhibit anti-tumor immune response and promote tumor angiogenesis and tumor invasion [ 245 , 246 ]. In ovarian cancer, MDSCs play an inhibitory role through prostaglandin E2 (PGE2), which not only enables normal dendritic cells (DCs) to differentiate into tolerogenic MDSCs, but also mediates MDSCs-derived PGE2 to directly inhibit CD8 + T cell function [ 235 , 247 ].…”

Section: Role Of Hif-α In Tumor Microenvironment Through Epigenetic Rmentioning

confidence: 99%

Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation

Mao

Wang

et al. 2020

J Exp Clin Cancer Res

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Hypoxia is the major influence factor in physiological and pathological courses which are mainly mediated by hypoxia-inducible factors (HIFs) in response to low oxygen tensions within solid tumors. Under normoxia, HIF signaling pathway is inhibited due to HIF-α subunits degradation. However, in hypoxic conditions, HIF-α is activated and stabilized, and HIF target genes are successively activated, resulting in a series of tumour-specific activities. The activation of HIFs, including HIF-1α, HIF-2α and HIF-3α, subsequently induce downstream target genes which leads to series of responses, the resulting abnormal processes or metabolites in turn affect HIFs stability. Given its functions in tumors progression, HIFs have been regarded as therapeutic targets for improved treatment efficacy. Epigenetics refers to alterations in gene expression that are stable between cell divisions, and sometimes between generations, but do not involve changes in the underlying DNA sequence of the organism. And with the development of research, epigenetic regulation has been found to play an important role in the development of tumors, which providing accumulating basic or clinical evidences for tumor treatments. Here, given how little has been reported about the overall association between hypoxic tumors and epigenetics, we made a more systematic review from epigenetic perspective in hope of helping others better understand hypoxia or HIF pathway, and providing more established and potential therapeutic strategies in tumors to facilitate epigenetic studies of tumors.

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Section: Role Of Hif-α In Tumor Microenvironment Through Epigenetic Rmentioning

confidence: 99%

Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation

Mao

Wang

et al. 2020

J Exp Clin Cancer Res

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“…Via a range of mechanisms, which include the generation of ROS and nitric oxide, arginine metabolism, induction of T regulatory cells and the production of anti-inflammatory cytokines, MDSC's are potent immune suppressors, inhibiting the proliferation and activation of innate (NK cells, DC's and macrophages) and adaptive (T and B cells) immune cells ( 227 , 228 ). Whilst the presence of MDSC's during acute inflammatory responses is seen as beneficial (due to their involvement in the resolution of inflammation), in the setting of chronic inflammation, where MDSC's persist, their suppressive activity is considered detrimental to the host ( 229 ). Thus, the elevated frequency of MDSC's reported in older adults, obese subjects and T2D patients ( 230 – 232 ) has been proposed as a potential mechanistic explanation for the increased susceptibility to infection and poor vaccination responses elicited by these individuals ( 233 , 234 ).…”

Section: Pathogen Eliminationmentioning

confidence: 99%

Immunesenescence: A Predisposing Risk Factor for the Development of COVID-19?

Hazeldine

Lord

2020

Front. Immunol.

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Bearing a strong resemblance to the phenotypic and functional remodeling of the immune system that occurs during aging (termed immunesenescence), the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), is characterized by an expansion of inflammatory monocytes, functional exhaustion of lymphocytes, dysregulated myeloid responses and the presence of highly activated senescent T cells. Alongside advanced age, male gender and pre-existing co-morbidities [e.g., obesity and type 2 diabetes (T2D)] are emerging as significant risk factors for COVID-19. Interestingly, immunesenescence is more profound in males when compared to females, whilst accelerated aging of the immune system, termed premature immunesenescence, has been described in obese subjects and T2D patients. Thus, as three distinct demographic groups with an increased susceptibility to COVID-19 share a common immune profile, could immunesenescence be a generic contributory factor in the development of severe COVID-19? Here, by focussing on three key aspects of an immune response, namely pathogen recognition, elimination and resolution, we address this question by discussing how immunesenescence may weaken or exacerbate the immune response to SARS-CoV-2. We also highlight how aspects of immunesenescence could render potential COVID-19 treatments less effective in older adults and draw attention to certain therapeutic options, which by reversing or circumventing certain features of immunesenescence may prove to be beneficial for the treatment of groups at high risk of severe COVID-19.

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“…MDSCs are immunosuppressive cells which could inhibit acute inflammatory reactions, trigger the resolution of inflammation and initiate the repair processes [24]. Recent studies have shown that MDSCs play important role in shaping T-cell responses [25,26].…”

Section: Discussionmentioning

confidence: 99%

NAD+ attenuates experimental autoimmune encephalomyelitis through induction of CD11b+ gr-1+ myeloid-derived suppressor cells

Wang

Tan

et al. 2020

Bioscience Reports

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Objective: To investigate the effects of nicotinamide adenine dinucleotide (NAD+) on the pathogenesis of the animal model for multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE). Methods: EAE model was induced by myelin oligodendrocyte protein (MOG 35-55). Clinical scores of EAE were measured in mice with or without NAD+ treatment. Hematoxylin and Eosin (HE) and Luxol Fast Blue (LFB) staining were performed to assess inflammation and demyelination, respectively. Expressions of target proteins were measured by Western blot. The numbers of myeloid-derived suppressor cells (MDSCs) were measured by immunofluorescent staining and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to measure the expressions of inflammatory cytokine in serum. Results: NAD+ treatment could decrease inflammatory cells and demyelination foci, attenuate the clinical scores of EAE and slightly delay disease onset. Western blot showed that NAD+ treatment up-regulated the expression of phosphorylated-STAT6 (p-STAT6) and SIRT1. Besides, NAD+ treatment up-regulated the expression of p-IκB and down-regulated the expression of p-NF-κB. In addition, NAD+ treatment could increase the numbers of CD11b+ gr-1+ MDSCs and the expression of Arginase-1. Moreover, NAD+ treatment up-regulated the expressions of IL-13 and down-regulated the expression of IFN-γ and IL-17. Conclusions: The present study demonstrated that NAD+ treatment may induce the CD11b+ gr-1+ MDSCs to attenuate EAE via activating the phosphorylation of STAT6 expression. Therefore, NAD+ should be considered as a potential novel therapeutic strategy for MS.

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The role of myeloid-derived suppressor cells (MDSC) in the inflammaging process

Cited by 83 publications

References 174 publications

Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation

Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation

Immunesenescence: A Predisposing Risk Factor for the Development of COVID-19?

NAD+ attenuates experimental autoimmune encephalomyelitis through induction of CD11b+ gr-1+ myeloid-derived suppressor cells

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