Insights into Myeloid-Derived Suppressor Cells in Inflammatory Diseases

Kwak, Yewon; Kim, Hye-Eun; Park, Sung‐Gyoo

doi:10.1007/s00005-015-0342-1

Cited by 31 publications

(35 citation statements)

References 176 publications

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“…Immunosuppressive cells have a fundamental role in the suppression of detrimental innate and adaptive immune responses and in the maintenance of immune self-tolerance. Overall, the activation of immunosuppressive cells, such as MDSCs and Tregs, has beneficial effects since it results in the resolution of acute inflammatory responses and the suppression of excessive inflammatory disorders, e.g., sepsis, autoimmune diseases, and transplantation [110,112,186]. However, in chronic inflammatory conditions, e.g.…”

Section: Chronic Immunosuppression Disturbs the Homeostasis Of Tissuesmentioning

confidence: 99%

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

2020

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The endoplasmic reticulum (ER) contains stress sensors which recognize the accumulation of unfolded proteins within the lumen of ER, and subsequently these transducers stimulate the unfolded protein response (UPR). The ER sensors include the IRE1, PERK, and ATF6 transducers which activate the UPR in an attempt to restore the quality of protein folding and thus maintain cellular homeostasis. If there is excessive stress, UPR signaling generates alarmins, e.g., chemokines and cytokines, which activate not only tissue-resident immune cells but also recruit myeloid and lymphoid cells into the affected tissues. ER stress is a crucial inducer of inflammation in many pathological conditions. A chronic low-grade inflammation and cellular senescence have been associated with the aging process and many age-related diseases, such as Alzheimer's disease. Currently, it is known that immune cells can exhibit great plasticity, i.e., they are able to display both pro-inflammatory and anti-inflammatory phenotypes in a context-dependent manner. The microenvironment encountered in chronic inflammatory conditions triggers a compensatory immunosuppression which defends tissues from excessive inflammation. Recent studies have revealed that chronic ER stress augments the suppressive phenotypes of immune cells, e.g., in tumors and other inflammatory disorders. The activation of immunosuppressive network, including myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg), has been involved in the aging process and Alzheimer's disease. We will examine in detail whether the ER stress-related changes found in aging tissues and Alzheimer's disease are associated with the activation of immunosuppressive network, as has been observed in tumors and many chronic inflammatory diseases.

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Section: Chronic Immunosuppression Disturbs the Homeostasis Of Tissuesmentioning

confidence: 99%

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

2020

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“…The first process is the expansion induced by various cytokines and growth factors produced in response to chronic stimulation, which involves factors like IL-6 and VEGF, and signaling pathways such as STAT3 and NF- κ B, which prevents maturation of myeloid cells. Then, a second activating signal provided by proinflammatory molecules to drive upregulation of arginase and iNOS and production of immune suppressive cytokines is required for their activation [130, 131]. In addition to above proposed pathways, it is reported that activated human HSCs during chronic inflammation induced mature peripheral blood monocytes into MDSCs, and, subsequently, excessive liver injury might be prevented by local induction of MDSCs.…”

Section: Immune Suppression: a Potential Linkage Of Oxidative Strementioning

confidence: 99%

“…In addition to above proposed pathways, it is reported that activated human HSCs during chronic inflammation induced mature peripheral blood monocytes into MDSCs, and, subsequently, excessive liver injury might be prevented by local induction of MDSCs. However, of note, in liver cancer patients, the expansion of HSC-induced MDSCs plays an opposite role to facilitate tumor growth by immune suppression [130, 131, 136]. …”

Section: Immune Suppression: a Potential Linkage Of Oxidative Strementioning

confidence: 99%

Insights into the Role and Interdependence of Oxidative Stress and Inflammation in Liver Diseases

Hong

Tan

et al. 2016

Oxidative Medicine and Cellular Longevity

264

179

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The crucial roles of oxidative stress and inflammation in the development of hepatic diseases have been unraveled and emphasized for decades. From steatosis to fibrosis, cirrhosis and liver cancer, hepatic oxidative stress, and inflammation are sustained and participated in this pathological progressive process. Notably, increasing evidences showed that oxidative stress and inflammation are tightly related, which are regarded as essential partners that present simultaneously and interact with each other in various pathological conditions, creating a vicious cycle to aggravate the hepatic diseases. Clarifying the interaction of oxidative stress and inflammation is of great importance to provide new directions and targets for developing therapeutic intervention. Herein, this review is concerned with the regulation and interdependence of oxidative stress and inflammation in a variety of liver diseases. In addition to classical mediators and signaling, particular emphasis is placed upon immune suppression, a potential linkage of oxidative stress and inflammation, to provide new inspiration for the treatment of liver diseases. Furthermore, since antioxidation and anti-inflammation have been extensively attempted as the strategies for treatment of liver diseases, the application of herbal medicines and their derived compounds that protect liver from injury via regulating oxidative stress and inflammation collectively were reviewed and discussed.

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“…In addition, because MDSCs are known to mediate T cell suppression through numerous genes, including ARG1, Nox2, IDO1, iNOS, PD-L1, HIF-1α, IL-4Rα, and MyD88, which reportedly involved in MDSC biology [27], we compared the expression levels of these genes by qRT-PCR in G-MDSCs and M-MDSCs isolated from PBMCs of 34 patients obtained at engraftment (Supplementary Figure S2). Among the target genes, ARG1 and Nox2 were significantly increased in G-MDSCs, whereas PD-L1 and HIF-1α were up-regulated in M-MDSCs.…”

Section: Cytokines and Known Factors Related To Mdsc Suppressive Actimentioning

confidence: 99%

Matrix Metalloproteinase-9 in Monocytic Myeloid-Derived Suppressor Cells Correlate with Early Infections and Clinical Outcomes in Allogeneic Hematopoietic Stem Cell Transplantation

Lee

Lim

Kim

et al. 2018

Biology of Blood and Marrow Transplantation

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The recovery of myeloid-derived suppressor cells (MDSCs) and its relevance in clinical acute graft-versus-host disease (GVHD) and post-hematopoietic stem cell transplantation (HSCT) infections remain to be fully characterized. We examined the expansion of circulating monocytic (M-) MDSCs and granulocytic (G-) MDSCs at the time of engraftment in 130 patients undergoing allogeneic HSCT (allo-HSCT). Compared with the G-MDSC group, the high M-MDSC group had a higher infection rate within 100 days, along with worse 1-year cumulative incidence of treatment-related mortality (TRM) and 2-year probability of event-free survival (EFS). The frequency of M-MDSCs was associated with preceding severe mucositis. Transcriptome profiling analysis of 2 isolated MDSC subtype showed significantly greater matrix metalloproteinase-9 (MMP-9) expression in M-MDSCs than in G-MDSCs. M-MDSCs produced abundantly more MMP-9. Importantly, compared with G-MDSCs, M-MDSCs isolated from patients post-HSCT had a greater capacity to suppress T cell responses, and MMP-9 blockade more forcefully inhibited their immunosuppressive effect. MMP-9 levels also were associated with the occurrence of infections and with transplantation outcomes. Based on these findings, we identify M-MDSCs as a major contributor to infections early after allo-HSCT and worse clinical outcomes via MMP-9.

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Insights into Myeloid-Derived Suppressor Cells in Inflammatory Diseases

Cited by 31 publications

References 176 publications

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

Insights into the Role and Interdependence of Oxidative Stress and Inflammation in Liver Diseases

Matrix Metalloproteinase-9 in Monocytic Myeloid-Derived Suppressor Cells Correlate with Early Infections and Clinical Outcomes in Allogeneic Hematopoietic Stem Cell Transplantation

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