Myeloid-derived suppressor cells coming of age

Nature Immunology, Journal Year: 2018, Volume and Issue: 19(2), P. 108 - 119

Published: Jan. 4, 2018

Language: Английский

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Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(8), P. 485 - 498

Published: Feb. 1, 2021

Language: Английский

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Ulcerative colitis

Nature Reviews Disease Primers, Journal Year: 2020, Volume and Issue: 6(1)

Published: Sept. 10, 2020

Language: Английский

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Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease

New England Journal of Medicine, Journal Year: 2020, Volume and Issue: 383(27), P. 2628 - 2638

Published: Oct. 27, 2020

Adult-onset inflammatory syndromes often manifest with overlapping clinical features. Variants in ubiquitin-related genes, previously implicated autoinflammatory disease, may define new disorders.We analyzed peripheral-blood exome sequence data independent of phenotype and inheritance pattern to identify deleterious mutations genes. Sanger sequencing, immunoblotting, immunohistochemical testing, flow cytometry, transcriptome cytokine profiling were performed. CRISPR-Cas9-edited zebrafish used as an vivo model assess gene function.We identified 25 men somatic affecting methionine-41 (p.Met41) UBA1, the major E1 enzyme that initiates ubiquitylation. (The UBA1 lies on X chromosome.) In such patients, fatal, treatment-refractory syndrome develops late adulthood, fevers, cytopenias, characteristic vacuoles myeloid erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous pulmonary inflammation, chondritis, vasculitis. Most these patients met criteria for (relapsing polychondritis, Sweet's syndrome, polyarteritis nodosa, or giant-cell arteritis) a hematologic condition (myelodysplastic multiple myeloma) both. Mutations found more than half hematopoietic stem including cells but not lymphocytes fibroblasts. p.Met41 resulted loss canonical cytoplasmic isoform expression novel, catalytically impaired initiated at p.Met67. Mutant showed decreased ubiquitylation activated innate immune pathways. Knockout homologue caused systemic inflammation.Using genotype-driven approach, we disorder connects seemingly unrelated adult-onset syndromes. We named this VEXAS (vacuoles, enzyme, X-linked, autoinflammatory, somatic) syndrome. (Funded by NIH Intramural Research Programs EU Horizon 2020 Innovation Program.).

Language: Английский

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Molecular mechanisms of ROS production and oxidative stress in diabetes

Biochemical Journal, Journal Year: 2016, Volume and Issue: 473(24), P. 4527 - 4550

Published: Dec. 9, 2016

Oxidative stress and chronic inflammation are known to be associated with the development of metabolic diseases, including diabetes. stress, an imbalance between oxidative antioxidative systems cells tissues, is a result over production oxidative-free radicals reactive oxygen species (ROS). One outcome excessive levels ROS modification structure function cellular proteins lipids, leading dysfunction impaired energy metabolism, altered cell signalling cycle control, transport mechanisms overall dysfunctional biological activity, immune activation inflammation. Nutritional such as that caused by excess high-fat and/or carbohydrate diets, promotes evident increased lipid peroxidation products, protein carbonylation decreased antioxidant status. In obesity, underlying factors lead pathologies insulin resistance, dysregulated pathways diabetes cardiovascular disease through metabolism resulting in secretion, action responses. However, exercise may counter thus improve inflammatory outcomes. present article, we review molecular origins significance production, targets responses describing how affects secretion action, from point view possible application novel diabetic therapies based on redox regulation.

Language: Английский

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DNA Damage and Repair Biomarkers of Immunotherapy Response

Cancer Discovery, Journal Year: 2017, Volume and Issue: 7(7), P. 675 - 693

Published: June 20, 2017

DNA-damaging agents are widely used in clinical oncology and exploit deficiencies tumor DNA repair. Given the expanding role of immune checkpoint blockade as a therapeutic strategy, interaction damage with system has recently come into focus, it is now clear that repair landscape an important driving response to blockade. Here, we summarize mechanisms by which genomic instability have been found shape antitumor describe efforts use biomarkers guide immune-directed therapies.

Language: Английский

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Targeting immunogenic cancer cell death by photodynamic therapy: past, present and future

Journal for ImmunoTherapy of Cancer, Journal Year: 2021, Volume and Issue: 9(1), P. e001926 - e001926

Published: Jan. 1, 2021

The past decade has witnessed major breakthroughs in cancer immunotherapy. This development been largely motivated by cell evasion of immunological control and consequent tumor resistance to conventional therapies. Immunogenic death (ICD) is considered one the most promising ways achieve total elimination. It activates T-cell adaptive immune response results formation long-term memory. ICD can be triggered many anticancer treatment modalities, including photodynamic therapy (PDT). In this review, we first discuss role PDT based on several classes photosensitizers, porphyrins non-porphyrins, critically evaluate their potential induction. We emphasize emerging trend induction combination with nanotechnology, which represents third-generation photosensitizers involves targeted PDT. However, also some limitations, reduced efficiency hypoxic microenvironment. Therefore, strategies for overcoming limitation, essential increasing efficiency. final part, suggest areas future research personalized immunotherapy, oxygen-boosted nanoparticles. conclusion, insights from last years increasingly support idea that a powerful strategy inducing experimental therapy. studies have focused mouse models, but it necessary validate clinical settings, will challenging area future.

Language: Английский

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Endoplasmic Reticulum Stress Causes Liver Cancer Cells to Release Exosomal miR‐23a‐3p and Up‐regulate Programmed Death Ligand 1 Expression in Macrophages

Hepatology, Journal Year: 2019, Volume and Issue: 70(1), P. 241 - 258

Published: March 11, 2019

Endoplasmic reticulum (ER) stress promotes tumor cell escape from immunosurveillance. However, the underlying mechanisms remain unknown. We hypothesized that ER induces hepatocellular carcinoma (HCC) cells to release exosomes, which attenuate antitumor immunity by modulating expression of programmed death ligand 1 (PD-L1) in macrophages. In this study, we demonstrated several markers (glucose-regulated protein 78, activating transcription factor 6, kinase R-like kinase, and inositol-requiring enzyme 1α) was up-regulated HCC tissues negatively correlated with overall survival clinicopathological scores patients HCC. Expression stress-related proteins positively CD68+ macrophage recruitment PD-L1 tissues. High-throughput sequencing analysis identified miR-23a-3p as one most abundant microRNAs exosomes derived tunicamycin (TM)-treated (Exo-TMs). levels survival. Treatment Exo-TMs macrophages vitro vivo. Bioinformatics suggests regulates through phosphatase tensin homolog (PTEN)-phosphatidylinositol 3-kinase-protein B (AKT) pathway. This notion confirmed transfection coculture experiments, revealed inhibited PTEN subsequently elevated phosphorylated AKT Finally, T Exo-TM-stimulated decreased CD8+ T-cell ratio interleukin-2 production but increased apoptosis vitro. Conclusion: ER-stressed up-regulate macrophages, inhibits function an exosome miR-23a-PTEN-AKT Our findings provide insight into mechanism how immunity.

Language: Английский

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Pharmacological targeting of endoplasmic reticulum stress in disease

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 21(2), P. 115 - 140

Published: Oct. 26, 2021

Language: Английский

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Targeting Mitochondria-Located circRNA SCAR Alleviates NASH via Reducing mROS Output

Cell, Journal Year: 2020, Volume and Issue: 183(1), P. 76 - 93.e22

Published: Sept. 14, 2020

Language: Английский

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