Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1α-dependent glycolysis

Lu, Yun; Liu, Huanrong; Bi, Yujing; Yang, Hui; Li, Yan; Wang, Jian; Zhang, Zhengguo; Wang, Yu; Li, Chunxiao; Jia, Anna; Han, Linian; Hu, Ying; Zhao, Yong; Wang, Ruoning; Liu, Guangwei

doi:10.1038/cmi.2017.5

Cited by 57 publications

(51 citation statements)

References 48 publications

(66 reference statements)

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“…SIRT1‐HIF‐1α axis plays an important role in regulating cellular metabolism. In our research, we found that SIRT1‐HIF‐1α axis is associated with the differentiation of several types of immune cells, including Th9 and MDSCs. Our team research showed that SIRT1 can deregulate function and differentiation of MDSCs through orchestrating HIF‐1α‐dependent glycolysis .…”

Section: Main Functional Characteristics Of Mdscsmentioning

confidence: 64%

Myeloid‐derived suppressor cells: Roles in the tumor microenvironment and tumor radiotherapy

Yin

Wang

et al. 2018

Intl Journal of Cancer

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Cancer progression is closely related to the tumor microenvironment in which the tumor exists, including surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, signaling molecules and the extracellular matrix. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can impact the growth and evolution of cancerous cells. One of major cell components in the tumor microenvironment is myeloid-derived suppressor cells (MDSCs), which promote tumor growth and metastasis directly or indirectly by recognizing other immune cells, producing cytokines and exerting their immunosuppression functions. MDSCs have emerged as major regulators of immune responses in cancer and key targets for treating cancer. There are many limitations and side-effect in approaches of conventional cancer therapy, including radiotherapy. It has grown up to be a burgeoning field that a combination of radiotherapy and immunotherapy applied to cancer therapy. Therefore, it is fundamental to explore the immune mechanism in the process of cancer treatment. Here, we reviewed the recent progress of MDSCs in roles of the tumor microenvironment and tumor radiotherapy.

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Section: Main Functional Characteristics Of Mdscsmentioning

confidence: 64%

Myeloid‐derived suppressor cells: Roles in the tumor microenvironment and tumor radiotherapy

Yin

Wang

et al. 2018

Intl Journal of Cancer

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“…For instance, glucocorticoids which are used routinely as firstline treatment and regulate transcription of many metabolic genes [91] associated with glycolytic, autophagy and mTOR pathways [92,93]. For instance, glucocorticoids which are used routinely as firstline treatment and regulate transcription of many metabolic genes [91] associated with glycolytic, autophagy and mTOR pathways [92,93].…”

Section: Targeting Metabolism In Rheumatoid Arthritismentioning

confidence: 99%

“…As highlighted above, studies examining metabolic pathways in RA have identified specific pathways, enzymes or metabolic intermediates that could potentially be targeted; however, many of our current treatment strategies are already known to alter metabolic pathways. For instance, glucocorticoids which are used routinely as firstline treatment and regulate transcription of many metabolic genes [91] associated with glycolytic, autophagy and mTOR pathways [92,93]. Conventional disease-modifying antirheumatic drugs (DMARDs) for RA and psoriatic arthritis (PsA), including methotrexate, leflunomide and apremilast, are anti-metabolic, where they target purine or pyrimidine nucleotide metabolism, the effects of which are known to inhibit both T cells and synovial fibroblast proliferation.…”

Section: Targeting Metabolism In Rheumatoid Arthritismentioning

confidence: 99%

Altered metabolic pathways regulate synovial inflammation in rheumatoid arthritis

Fearon

Hanlon

Wade

et al. 2018

Clinical and Experimental Immunology

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Rheumatoid arthritis is characterized by synovial proliferation, neovascularization and leucocyte extravasation leading to joint destruction and functional disability. The blood vessels in the inflamed synovium are highly dysregulated, resulting in poor delivery of oxygen; this, along with the increased metabolic demand of infiltrating immune cells and inflamed resident cells, results in the lack of key nutrients at the site of inflammation. In these adverse conditions synovial cells must adapt to generate sufficient energy to support their proliferation and activation status, and thus switch their cell metabolism from a resting regulatory state to a highly metabolically active state. This alters redox-sensitive signalling pathways and also results in the accumulation of metabolic intermediates which, in turn, can act as signalling molecules that further exacerbate the inflammatory response. The RA synovium is a multi-cellular tissue, and while many cell types interact to promote the inflammatory response, their metabolic requirements differ. Thus, understanding the complex interplay between hypoxia-induced signalling pathways, metabolic pathways and the inflammatory response will provide better insight into the underlying mechanisms of disease pathogenesis. OTHER ARTICLES PUBLISHED IN THIS REVIEW SERIESTranslating immunometabolism: towards curing human diseases by targeting metabolic processes underpinning the immune response. Clinical and Experimental Immunology 2019, 197: 141-142. T cell metabolism in chronic viral infection. Clinical and Experimental Immunology 2019, 197: 143-152. Sculpting tumor microenvironment with immune system: from immunometabolism to immunoediting. Clinical and Experimental Immunology 2019, 197: 153-160. Sensing between reactions -how the metabolic microenvironment shapes immunity.

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“…Glucocorticoids have revolutionized the treatment of patients with arthritis and other inflammatory diseases since the mid‐20th century . They bind to the glucocorticoid receptor and regulate transcription of genes involved in metabolism . The efficacy of glucocorticoids has been linked to inhibition of glycolysis , while the stimulation of autophagy and mTOR activity are mechanisms that have been identified as underlying the resistance to glucocorticoids.…”

Section: Metabolic Targets Of Treatment In Rheumatic Diseasesmentioning

confidence: 99%

Review: Metabolic Control of Immune System Activation in Rheumatic Diseases

Perl

2017

Arthritis & Rheumatology

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Metabolic pathways mediate lineage specification within the immune system through the regulation of glucose utilization, a process that generates energy in the form of ATP and synthesis of amino acids, nucleotides, and lipids to enable cell growth, proliferation, and survival. CD4+ T cells, a proinflammatory cell subset, preferentially produce ATP through glycolysis, whereas cells with an antiinflammatory lineage, such as memory and regulatory T cells, favor mitochondrial ATP generation. In conditions of metabolic stress or a shortage of nutrients, cells rely on autophagy to secure amino acids and other substrates, while survival depends on the sparing of mitochondria and maintenance of a reducing environment. The pentose phosphate pathway acts as a key gatekeeper of inflammation by supplying ribose‐5‐phosphate for cell proliferation and NADPH for antioxidant defenses. Increased lysosomal catabolism, accumulation of branched amino acids, glutamine, kynurenine, and histidine, and depletion of glutathione and cysteine activate the mechanistic target of rapamycin (mTOR), an arbiter of lineage development within the innate and adaptive immune systems. Mapping the impact of susceptibility genes to metabolic pathways allows for better understanding and therapeutic targeting of disease‐specific expansion of proinflammatory cells. Therapeutic approaches aimed at glutathione depletion and mTOR pathway activation appear to be safe and effective for treating lupus, while an opposing intervention may be of benefit in rheumatoid arthritis. Environmental sources of origin for metabolites within immune cells may include microbiota and plants. Thus, a better understanding of the pathways of immunometabolism could provide new insights into the pathogenesis and treatment of the rheumatic diseases.

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Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1α-dependent glycolysis

Cited by 57 publications

References 48 publications

Myeloid‐derived suppressor cells: Roles in the tumor microenvironment and tumor radiotherapy

Myeloid‐derived suppressor cells: Roles in the tumor microenvironment and tumor radiotherapy

Altered metabolic pathways regulate synovial inflammation in rheumatoid arthritis

Review: Metabolic Control of Immune System Activation in Rheumatic Diseases

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