cGAS-STING DNA-sensing in inflammatory bowel diseases

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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Cell-Autonomous Immunity: From Cytosolic Sensing to Self-Defense

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4025 - 4025

Published: April 24, 2025

As an evolutionarily conserved and ubiquitous mechanism of host defense, non-immune cells in vertebrates possess the intrinsic ability to autonomously detect combat intracellular pathogens. This process, termed cell-autonomous immunity, is distinct from classical innate immunity. In this review, we comprehensively examine defense mechanisms employed by response pathogen invasion. We provide a detailed analysis cytosolic sensors that recognize aberrant nucleic acids, lipopolysaccharide (LPS), other pathogen-associated molecular patterns (PAMPs). Specifically, elucidate underlying key signaling pathways, including cyclic GMP-AMP synthase (cGAS)-stimulator interferon genes (STING) pathway, retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-mitochondrial antiviral (MAVS) axis, guanylate-binding proteins (GBPs)-mediated pathway. Furthermore, critically evaluate involvement these pathways pathogenesis various diseases, autoimmune disorders, inflammatory conditions, malignancies, while highlighting their potential as therapeutic targets.

Language: Английский

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Recent advancements in cGAS-STING activation, tumor immune evasion, and therapeutic implications

Medical Oncology, Journal Year: 2024, Volume and Issue: 41(11)

Published: Oct. 18, 2024

Language: Английский

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The Potential of Anti-Inflammatory DC Immunotherapy in Improving Proteinuria in Type 2 Diabetes Mellitus

Vaccines, Journal Year: 2024, Volume and Issue: 12(9), P. 972 - 972

Published: Aug. 27, 2024

A typical consequence of type 2 diabetes mellitus, diabetic kidney disease (DKD) is a significant risk factor for end-stage renal disease. The pathophysiology mainly associated with the immune system, which involves adhesion molecules and growth factors disruption, excessive expression inflammatory mediators, decreased levels anti-inflammatory cell infiltration in kidney. Dendritic cells are professional antigen-presenting acting as bridge connecting innate adaptive responses. subset DCs also capable modulating inflammation. Autologous dendritic can be made by vitro differentiation peripheral blood monocytes utilized cell-based therapy. Treatment cytokines, immunosuppressants, substances derived from pathogens induce tolerogenic or features ex vivo–generated DCs. It has been established that targeting inflammation alleviate progression DKD. Recent studies have focused on potential cell–based therapies to modulate responses favorably. By inducing phenotype cells, it possible decrease response subsequent damage. This article highlights possibility using therapy DKD through its role controlling

Language: Английский

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Epigenetic regulation of cGAS and STING expression in cancer

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 138, P. 112556 - 112556

Published: June 26, 2024

Language: Английский

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CRISPR-Mediated Construction of Gene-Knockout Mice for Investigating Antiviral Innate Immunity

Methods in molecular biology, Journal Year: 2024, Volume and Issue: unknown, P. 61 - 74

Published: Aug. 27, 2024

Language: Английский

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Lymph node-targeted STING agonist nanovaccine against chronic HBV infection

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Aug. 28, 2024

Chronic hepatitis B virus (HBV) infection is a global health problem that substantially increases the risk of developing liver disease. The development novel strategy to induce anti-HB seroconversion and achieve long-lasting immune response against chronic HBV remains challenging. Here, we found affected signaling pathway involved in STING-mediated induction host responses dendritic cells (DCs) then generated lymph node-targeted nanovaccine co-delivered surface antigen (HBsAg) cyclic diguanylate monophosphate (c-di-GMP) (named PP-SG nanovaccine). feasibility efficiency for CHB treatment were evaluated HBV-carrier mice. Serum samples analyzed HBsAg, anti-HBs, DNA, alanine aminotransferase levels, DNA RNA HBcAg, accompanied by an analysis HBV-specific cellular humoral during treatment. increased phagocytosis DC maturation, efficiently safely eliminated HBV, achieved reinjection, disrupted infection-induced tolerance, as characterized generation multifunctionality CD8

Language: Английский

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High levels of tumor cell-intrinsic STING signaling are associated with increased infiltration of CD8+ T cells in dMMR/MSI-H gastric cancer

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 6, 2024

Language: Английский

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The Role of STING-Mediated Activation of Dendritic Cells in Cancer Immunotherapy

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 10685 - 10697

Published: Oct. 1, 2024

The signaling pathway that comprises cyclic guanosine monophosphate-adenosine monophosphate (cGAMP or GMP-AMP) synthase (cGAS) and Stimulator of Interferon Genes (STING) is emerging as a druggable target for immunotherapy, with tumor-resident dendritic cells (DC) playing critical role in mediating its effects. STING receptor part the DNA-sensing cellular machinery, can trigger secretion pro-inflammatory mediators, priming effector T initiating specific antitumor responses. Yet, recent studies have highlighted dual activation context cancer: either promote responses enhance tumor progression. This dichotomy often depends on cell type which cGAS-STING induced mode, namely acute versus chronic. Of note, at DC level appears to be particularly important eradication. review outlines contribution different conventional plasmacytoid subsets describes mechanisms underlying STING-mediated DCs cancer. We further highlight how plays an intricate modulating function embedded tissue. Additionally, we discuss strategies being employed harness cancer treatment, such development synthetic agonists nano-based delivery systems, spotlighting current techniques used prompt engagement specifically DCs.

Language: Английский

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Enhanced Tumor Immunotherapy by Triple Amplification Effects of Nanomedicine on the STING Signaling Pathway in Dendritic Cells

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Abstract Insufficient activation of stimulator interferon genes (STING) signaling pathway in tumor‐associated dendritic cells limits the efficiency tumor immunotherapy. Herein, “three‐in‐one” IAHA‐LaP/siPTPN6 NPs containing lanthanum ions (La 3+ ), cGAMP, and PTPN6 siRNA are developed for triple amplification STING pathway. In vitro results demonstrate that La significantly promotes cGAMP‐mediated by enhancing phosphorylation STING, TBK1, IRF3, NF‐ κ B p65. Moreover, further enhance p65 augment K63‐linked ubiquitination protein via siPTPN6‐mediated downregulation SHP‐1 protein. Furthermore, improve secretion IFN β (2.4‐fold), IL‐6 (1.5‐fold), TNF‐ α (1.4‐fold), thereby promoting DCs maturation compared to mixture cGAMP. vivo show remarkably inhibit primary growth increasing percentage mature tumor‐draining lymph nodes, polarizing M2/M1 phenotype TME, infiltration CD8 + T into tumors. these dramatically prevent distal inducing systemic anti‐tumor immunity generating a long‐term memory protection against recurrence mice bearing bilateral B16F10. These may offer promising platform robust immune responses.

Language: Английский

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