Emerging role of the cGAS-STING signaling pathway in autoimmune diseases: Biologic function, mechanisms and clinical prospection

Hu, Ying; Chen, Bangjie; Yang, Fan; Su, Yiyi; Yang, Dashuai; Yao, Yan; Wang, Shuxian; Wu, Yincui; Tao, Liangsong; Xu, Tao

doi:10.1016/j.autrev.2022.103155

Cited by 42 publications

(16 citation statements)

References 92 publications

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Section: Resultsmentioning

confidence: 99%

“…Moreover, abnormal activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) signaling pathway has been implicated in the development of RA. [49] Glucocorticoids, such as cortisol, are released in response to pro-inflammatory events to reduce inflammation by promoting the apoptosis of pro-inflammatory T-cells, inhibiting the production of B-cell antibodies, and reducing neutrophil migration. [50] Interestingly, glucocorticoids also play a role in sleep regulation.…”

Section: The Effects Of Sleep Deprivation On the Progression Of Autoi...mentioning

confidence: 99%

“…This, in turn, activates the cGAS-STING innate immune signaling pathway, which is known to be active in SLE and other autoimmune diseases. [49,60] SLE-associated dysregulated pathways have been linked to circadian abnormalities. Patients with SLE or those at risk of developing it often experience sleep disruptions, which significantly impact their quality of life.…”

Section: The Effects Of Sleep Deprivation On the Progression Of Autoi...mentioning

confidence: 99%

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Circadian rhythm in systemic autoimmune conditions: Potential of chrono-immunology in clinical practice: A narrative review

et al. 2023

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The circadian rhythm (CR) is a fundamental biological process regulated by the Earth’s rotation and solar cycles. It plays a critical role in various bodily functions, and its dysregulation can have systemic effects. These effects impact metabolism, redox homeostasis, cell cycle regulation, gut microbiota, cognition, and immune response. Immune mediators, cycle proteins, and hormones exhibit circadian oscillations, supporting optimal immune function and defence against pathogens. Sleep deprivation and disruptions challenge the regulatory mechanisms, making immune responses vulnerable. Altered CR pathways have been implicated in diseases such as diabetes, neurological conditions, and systemic autoimmune diseases (SADs). SADs involve abnormal immune responses to self-antigens, with genetic and environmental factors disrupting self-tolerance and contributing to conditions like Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Inflammatory Myositis. Dysregulated CR may lead to increased production of pro-inflammatory cytokines, contributing to the systemic responses observed in SADs. Sleep disturbances significantly impact the quality of life of patients with SADs; however, they are often overlooked. The relationship between sleep and autoimmune conditions, whether causal or consequential to CR dysregulation, remains unclear. Chrono-immunology investigates the role of CR in immunity, offering potential for targeted therapies in autoimmune conditions. This paper provides an overview of the connections between sleep and autoimmune conditions, highlighting the importance of recognizing sleep disturbances in SADs and the need for further research into the complex relationship between the CR and autoimmune diseases.

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Section: Resultsmentioning

confidence: 99%

Section: The Effects Of Sleep Deprivation On the Progression Of Autoi...mentioning

confidence: 99%

Section: The Effects Of Sleep Deprivation On the Progression Of Autoi...mentioning

confidence: 99%

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Circadian rhythm in systemic autoimmune conditions: Potential of chrono-immunology in clinical practice: A narrative review

et al. 2023

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“…Similar to CLEC5A, cyclic guanosine monophosphate (GMP) -adenosine monophosphate (AMP) synthase (cGAS) is also a member of PRR to act as an additional first-line host immune defense that can induce type I IFN response through its interaction with downstream stimulator of interferon genes (STING), i.e., the cGAS-STING pathway [63]. Recently, many immunological studies have focused on the cGAS-STING pathway as another player in the pathogenesis of autoimmune diseases, including SLE [64]. It is speculated that cGAS could sense and interact with free plasma intrinsic or extrinsic DNA fragments derived from engulfed NETs to trigger immune cascade [65].…”

Section: Discussionmentioning

confidence: 99%

The Role of Plasma Cell-Free Mitochondrial DNA and Nuclear DNA in Systemic Lupus Erythematosus

Lee¹,

Lin²,

Pan³

et al. 2022

Front. Biosci. (Landmark Ed)

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Background:The roles of plasma cell-free (pcf) mitochondrial DNA (mtDNA pcf ) and nuclear DNA (nDNA pcf ) in the pathogenesis of systemic lupus erythematosus (SLE) remain unclear. We analyzed the relative copies of mtDNA pcf and nDNA pcf and investigated their association with the levels of plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG), plasma malondialdehyde (MDA) and mRNA of leukocyte C-type lectin domain family 5 member A (CLEC5A) in SLE patients. Methods: A total of 80 SLE patients and 43 healthy controls (HCs) were enrolled. Their plasma samples were subjected to the measurements of mtDNA pcf copies, nDNA pcf copies, 8-OHdG and MDA, respectively. Their leukocytes were analyzed for CLEC5A mRNA expression. Results: SLE patients had higher nDNA pcf copies (2.84 ± 1.99 vs. 2.00 ± 0.88, p = 0.002), lower mtDNA pcf copies (4.81 ± 6.33 vs. 9.83 ± 14.20, p = 0.032), higher plasma 8-OHdG (0.227 ± 0.085 vs. 0.199 ± 0.041 ng/mL, p = 0.016), lower plasma MDA (3.02 ± 2.20 vs. 4.37 ± 2.16 µM, p = 0.001) and similar leukocyte CLEC5A mRNA expression levels (1.21 ± 1.17 vs. 1.26 ± 1.05, p = 0.870), as compared with those of HCs. Among the HCs, SLE patients with SLE Disease Activity Index (SLEDAI) ≤8, and SLE patients with SLEDAI >8, their respective mtDNA pcf copies decreased stepwisely (9.83 ± 14.20 vs. 6.28 ± 7.91 vs. 3.19 ± 3.35, p = 0.054). The nDNA pcf copies of HCs, SLE patients without nephritis, and SLE patients with nephritis were increased stepwisely (2.00 ± 0.88 vs. 2.63 ± 1.74 vs. 3.16 ± 2.34, p = 0.043). Among SLE patients, higher nDNA pcf copies were associated with higher levels of plasma 8-OHdG (p < 0.001) but lower plasma MDA (p = 0.019). Among HCs but not SLE patients, higher nDNA pcf copies (p = 0.013) or lower mtDNA pcf copies (p < 0.001) were related to higher levels of leukocyte CLEC5A mRNA expression. Conclusions: Higher nDNA pcf , lower mtDNA pcf , increased ROS-elicited oxidative DNA damage and dysregulated leukocyte CLEC5A expression might be implicated in the pathogenesis of SLE.Keywords: plasma cell-free mitochondrial DNA (mtDNA pcf ); plasma cell-free nuclear DNA (nDNA pcf ); malondialdehyde (MDA); 8-hydroxy-2'-deoxyguanosine (8-OHdG); C-type lectin domain family 5 member A (CLEC5A); systemic lupus erythematosus (SLE)

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“…The cGAS-STING-IKK signaling pathway, together with IRF3, induces classical NF-kB function, starts the transcription of immune stimulating gene, and passes the non classical NF-kB Pathway participate in other important activities (28,37,38,41). cGAS recognizes abnormal exogenous and endogenous DNA, promotes activation of multiple immune stimulators, autophagy, remodeling of tumor environment, and production of inflammatory factors through cGAS-STING signal pathway, and plays an important role in inflammation, autoimmunity, anti-tumor, anti-bacterial, and viral infection (28,32,33,38,(42)(43)(44)(45)(46). cGAMP is a kind of cyclic dinucleotide (CDN) formed by the connection of GTP and ATP through phosphodiester bond.…”

Section: Signaling Processes and Functions Of Cgas-sting Pathwaymentioning

confidence: 99%

Advances of MnO2 nanomaterials as novel agonists for the development of cGAS-STING-mediated therapeutics

Zhang

et al. 2023

Front. Immunol.

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As an essential micronutrient, manganese plays an important role in the physiological process and immune process. In recent decades, cGAS-STING pathway, which can congenitally recognize exogenous and endogenous DNA for activation, has been widely reported to play critical roles in the innate immunity against some important diseases, such as infections and tumor. Manganese ion (Mn2+) has been recently proved to specifically bind with cGAS and activate cGAS-STING pathway as a potential cGAS agonist, however, is significantly restricted by the low stability of Mn2+ for further medical application. As one of the most stable forms of manganese, manganese dioxide (MnO2) nanomaterials have been reported to show multiple promising functions, such as drug delivery, anti-tumor and anti-infection activities. More importantly, MnO2 nanomaterials are also found to be a potential candidate as cGAS agonist by transforming into Mn2+, which indicates their potential for cGAS-STING regulations in different diseased conditions. In this review, we introduced the methods for the preparation of MnO2 nanomaterials as well as their biological activities. Moreover, we emphatically introduced the cGAS-STING pathway and discussed the detailed mechanisms of MnO2 nanomaterials for cGAS activation by converting into Mn2+. And we also discussed the application of MnO2 nanomaterials for disease treatment by regulating cGAS-STING pathway, which might benefit the future development of novel cGAS-STING targeted treatments based on MnO2 nanoplatforms.

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Emerging role of the cGAS-STING signaling pathway in autoimmune diseases: Biologic function, mechanisms and clinical prospection

Cited by 42 publications

References 92 publications

Circadian rhythm in systemic autoimmune conditions: Potential of chrono-immunology in clinical practice: A narrative review

Circadian rhythm in systemic autoimmune conditions: Potential of chrono-immunology in clinical practice: A narrative review

The Role of Plasma Cell-Free Mitochondrial DNA and Nuclear DNA in Systemic Lupus Erythematosus

Advances of MnO2 nanomaterials as novel agonists for the development of cGAS-STING-mediated therapeutics

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