STING-dependent cytosolic DNA sensor pathways regulate NKG2D ligand expression

Bert, Nina Le; Lam, Adeline R.; Ho, Samantha S.W.; Shen, Yu; Liu, Mo; Gasser, Stephan

doi:10.4161/onci.29259

Cited by 20 publications

(16 citation statements)

References 9 publications

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“…Of note, as shown in studies on tumor models, DDR reportedly induces the expression of numerous class III DAMPs including MICs and different ULBPs through the activation of STING‐mediated pathways . Strikingly, the data suggest that DNA damage in lymphoma cells leads to the presence of class I DAMPs in form of cytosolic single‐stranded DNA and dsDNA.…”

Section: The Dna Damage Responsementioning

confidence: 66%

“…Other lines of study lend support to the suggestion that DNA damage or DNA replication stress promotes release of aberrant DNA structures into the cytosol in the form of single‐stranded (ss) and double‐stranded (ds) DNA breaks that operate as class I DAMPs. They are sensed by the DNA receptor cyclic GMP‐AMP synthase and probably other as‐yet unidentified DNA receptors to activate stimulator of interferon genes (STING)–dependent pathways to promote defense pathways .…”

Section: The Dna Damage Responsementioning

confidence: 99%

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Transplantation and Damage-Associated Molecular Patterns (DAMPs)

Land

Agostinis

Gasser

et al. 2016

American Journal of Transplantation

131

110

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Upon solid organ transplantation and during cancer immunotherapy, cellular stress responses result in the release of damage-associated molecular patterns (DAMPs). The various cellular stresses have been characterized in detail over the last decades, but a unifying classification based on clinically important aspects is lacking. Here, we provide an in-depth review of the most recent literature along with a unifying concept of the danger/injury model, suggest a classification of DAMPs, and review the recently elaborated mechanisms that result in the emission of such factors. We further point out the differences in DAMP responses including the release following a heat shock pattern, endoplasmic reticulum stress, DNA damage-mediated DAMP release, and discuss the diverse pathways of regulated necrosis in this respect. The understanding of various forms of DAMPs and the consequences of their different release patterns are prerequisite to associate serum markers of cellular stresses with clinical outcomes.

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Section: The Dna Damage Responsementioning

confidence: 66%

Section: The Dna Damage Responsementioning

confidence: 99%

Transplantation and Damage-Associated Molecular Patterns (DAMPs)

Land

Agostinis

Gasser

et al. 2016

American Journal of Transplantation

131

110

View full text Add to dashboard Cite

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“…However, this is not the only way whereby the transition from the adaptive arm of stress responses to the activation of RCD contributes to the maintenance of the entire organism. Indeed, both stressed and dying cells emit a large panel of signals that alert other cells of danger, including various cytokines and so-called "damage-associated molecular patterns" (DAMPs) [41][42][43].…”

Section: Regulated Cell Death and Organismal Homeostasismentioning

confidence: 99%

Regulated cell death and adaptive stress responses

Galluzzi¹,

Pedro²,

Kepp³

et al. 2016

Cell. Mol. Life Sci.

142

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Eukaryotic cells react to potentially dangerous perturbations of the intracellular or extracellular microenvironment by activating rapid (transcription-independent) mechanisms that attempt to restore homeostasis. If such perturbations persist, cells may still try to cope with stress by activating delayed and robust (transcription-dependent) adaptive systems, or they may actively engage in cellular suicide.This regulated form of cell death can manifest with various morphological, biochemical and immunological correlates, and constitutes an ultimate attempt of stressed cells to maintain organismal homeostasis. Here, we dissect the general organization of adaptive cellular responses to stress, their intimate connection with regulated cell death, and how the latter operates for the preservation of organismal homeostasis.3

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“…These data suggested that induced DNA damage, via the cytosolic DNA sensing pathway, upregulates NKG2D ligands in cell lines that express low amounts of ligands. Furthermore, DNA damage associated with tumorigenesis appears to also activate the cytosolic DNA sensing pathway and sustains constitutive expression of NKG2D ligands in tumor cells . The mediators that link the cGAS‐STING‐IRF3 pathway to NKG2D ligand expression on the cell surface remain to be established.…”

Section: Genomic Damage Regulates Nkg2d Ligandsmentioning

confidence: 99%

“…Furthermore, DNA damage associated with tumorigenesis appears to also activate the cytosolic DNA sensing pathway and sustains constitutive expression of NKG2D ligands in tumor cells. [40][41][42] The mediators that link the T A B L E 1 Regulation of cellular expression of NKG2D ligands by stress pathways F I G U R E 1 Summary of pathways and signals discussed in this review that induce NK cell activation and/or NKG2D ligand expression in tumor cells and in virus-infected cells. The pathways include the DNA damage response, the cGAS-STING pathway, proliferative signals, PI3-kinase activity, dysregulation of histone acetylation, and the integrated stress response.…”

Section: Genomic Damage Regulates Nkg2d Ligandsmentioning

confidence: 99%

Dysregulated cellular functions and cell stress pathways provide critical cues for activating and targeting natural killer cells to transformed and infected cells

Raulet

Marcus

Coscoy

2017

Immunological Reviews

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Summary Natural killer (NK) cells recognize and kill cancer cells and infected cells by engaging cell surface ligands that are induced preferentially or exclusively on these cells. These ligands are recognized by activating receptors on NK cells, such as NKG2D. In addition to activation by cell surface ligands, the acquisition of optimal effector activity by NK cells is driven in vivo by cytokines and other signals. This review addresses a developing theme in NK cell biology: that NK-activating ligands on cells, and the provision of cytokines and other signals that drive high effector function in NK cells, are driven by abnormalities that arise from transformation or the infected state. The pathways include genomic damage, which causes self DNA to be exposed in the cytosol of affected cells, where it activates the DNA sensor cGAS. The resulting signaling induces NKG2D ligands and also mobilizes NK cell activation. Other key pathways that regulate NKG2D ligands include PI-3 kinase activation, histone acetylation, and the integrated stress response. This review summarizes the roles of these pathways and their relevance in both viral infections and cancer.

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STING-dependent cytosolic DNA sensor pathways regulate NKG2D ligand expression

Cited by 20 publications

References 9 publications

Transplantation and Damage-Associated Molecular Patterns (DAMPs)

Transplantation and Damage-Associated Molecular Patterns (DAMPs)

Regulated cell death and adaptive stress responses

Dysregulated cellular functions and cell stress pathways provide critical cues for activating and targeting natural killer cells to transformed and infected cells

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