Dendritic cell subsets in cancer immunity and tumor antigen sensing

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 20(5), P. 432 - 447

Published: March 22, 2023

Abstract Dendritic cells (DCs) exhibit a specialized antigen-presenting function and play crucial roles in both innate adaptive immune responses. Due to their ability cross-present tumor cell-associated antigens naïve T cells, DCs are instrumental the generation of specific T-cell-mediated antitumor effector responses control growth cell dissemination. Within an immunosuppressive microenvironment, DC functions can, however, be severely impaired. In this review, we focus on mechanisms capture activation by role microenvironment shaping functions, taking advantage recent studies showing phenotype acquisition, transcriptional state functional programs revealed scRNA-seq analysis. The therapeutic potential DC-mediated antigen sensing priming immunity is also discussed.

Language: Английский

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Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: June 28, 2021

Remarkable progress in ageing research has been achieved over the past decades. General perceptions and experimental evidence pinpoint that decline of physical function often initiates by cell senescence organ ageing. Epigenetic dynamics immunometabolic reprogramming link to alterations cellular response intrinsic extrinsic stimuli, representing current hotspots as they not only (re-)shape individual identity, but also involve fate decision. This review focuses on present findings emerging concepts epigenetic, inflammatory, metabolic regulations consequences process. Potential therapeutic interventions targeting regulatory mechanisms, using state-of-the-art techniques are discussed.

Language: Английский

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Signaling pathways of chronic kidney diseases, implications for therapeutics

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 9, 2022

Abstract Chronic kidney disease (CKD) is a chronic renal dysfunction syndrome that characterized by nephron loss, inflammation, myofibroblasts activation, and extracellular matrix (ECM) deposition. Lipotoxicity oxidative stress are the driving force for loss of including tubules, glomerulus, endothelium. NLRP3 inflammasome signaling, MAPK PI3K/Akt RAAS signaling involves in lipotoxicity. The upregulated Nox expression decreased Nrf2 result directly. injured resident cells release proinflammatory cytokines chemokines to recruit immune such as macrophages from bone marrow. NF-κB JAK-STAT Toll-like receptor cGAS-STING major pathways mediate inflammation inflammatory cells. produce secret great number profibrotic TGF-β1, Wnt ligands, angiotensin II. TGF-β Notch evoke activation promote generation ECM. potential therapies targeted these also introduced here. In this review, we update key lipotoxicity, stress, kidneys with injury, drugs based on latest studies. Unifying will be instrumental advance further basic clinical investigation CKD.

Language: Английский

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Intranasal COVID-19 vaccines: From bench to bed

EBioMedicine, Journal Year: 2022, Volume and Issue: 76, P. 103841 - 103841

Published: Jan. 24, 2022

Language: Английский

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Mitochondrial dysfunction: mechanisms and advances in therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 15, 2024

Abstract Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation disease progression. Particularly, mitochondrial dysfunctions identified many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, cancer. However, the multifaceted nature elusive phenotypic threshold dysfunction complicate our understanding contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among most important therapeutic targets. In recent years, strategies targeting have continuously emerged transitioned clinical trials. Advanced intervention such as using healthy replenish or replace damaged mitochondria, has shown promise preclinical trials various Mitochondrial components, mtDNA, mitochondria-located microRNA, associated proteins can be potential agents augment function immunometabolic diseases tissue injuries. Here, we review current knowledge pathophysiology concrete examples We also summarize treat perspective dietary supplements targeted therapies, well translational situation related pharmacology agents. Finally, this discusses innovations applications transplantation an advanced promising treatment.

Language: Английский

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The interaction between ferroptosis and inflammatory signaling pathways

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(3)

Published: March 21, 2023

Abstract Ferroptosis is an iron-dependent regulated cell death driven by excessive lipid peroxidation. Inflammation one common and effective physiological event that protects against various stimuli to maintain tissue homeostasis. However, the dysregulation of inflammatory responses can cause imbalance immune system, dysfunction death. Recent studies have pointed out activation inflammation, including multiple inflammation-related signaling pathways, lead ferroptosis. Among related signal transduction we focused on five classical namely, JAK-STAT, NF-κB, inflammasome, cGAS-STING MAPK expounded their roles in To date, many agents shown therapeutic effects ferroptosis-related diseases modulating aforementioned pathways vivo vitro. Moreover, regulatory these iron metabolism peroxidation been described detail, contributing further understanding pathophysiological process Taken together, targeting inflammation will provide appropriate ways intervene ferroptosis diseases.

Language: Английский

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SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB

Communications Biology, Journal Year: 2022, Volume and Issue: 5(1)

Published: Jan. 12, 2022

SARS-CoV-2 is a novel virus that has rapidly spread, causing global pandemic. In the majority of infected patients, leads to mild disease; however, in significant proportion infections, individuals develop severe symptoms can lead long-lasting lung damage or death. These cases are often associated with high levels pro-inflammatory cytokines and low antiviral responses, which cause systemic complications. Here, we have evaluated transcriptional cytokine secretion profiles detected distinct upregulation inflammatory cell cultures samples taken from patients. Building on these observations, found specific activation NF-κB block IRF3 nuclear translocation cells. This response was mediated by cGAS-STING could be attenuated through several STING-targeting drugs. Our results show directs mediated, NF-κB-driven immune human epithelial cells likely contributes responses seen patients therapeutically targeted suppress disease symptoms.

Language: Английский

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Signalling mechanisms and cellular functions of SUMO

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(11), P. 715 - 731

Published: June 24, 2022

Language: Английский

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XBP1 deficiency promotes hepatocyte pyroptosis by impairing mitophagy to activate mtDNA-cGAS-STING signaling in macrophages during acute liver injury

Redox Biology, Journal Year: 2022, Volume and Issue: 52, P. 102305 - 102305

Published: March 28, 2022

Hepatocellular cell death and macrophage proinflammatory activation contribute to the pathology of various liver diseases, during which XBP1 plays an important role. However, function mechanism in thioacetamide (TAA)-induced acute injury (ALI) remains unknown. Here, we investigated effects inhibition on promoting hepatocellular pyroptosis activate STING signaling ALI. While both TAA- LPS-induced ALI triggered hepatocytes, hepatocyte-specific knockout mice exhibited exacerbated with increased enhanced activation. Mechanistically, mtDNA released from TAA-stressed hepatocytes could be engulfed by macrophages, further inducing a cGAS- dose-dependent manner. deficiency ROS production promote activating NLRP3/caspase-1/GSDMD signaling, facilitated extracellular release mtDNA. Moreover, impaired mitophagy was found deficient reversed PINK1 overexpression. Mitophagy restoration also inhibited mice. Activation XBP1-mediated pathway were observed human livers Collectively, these findings demonstrate that promotes hepatocyte impairing mtDNA/cGAS/STING providing potential therapeutic targets for

Language: Английский

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Cellular functions of cGAS-STING signaling

Trends in Cell Biology, Journal Year: 2022, Volume and Issue: 33(8), P. 630 - 648

Published: Nov. 24, 2022

Language: Английский

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