DNA-dependent Activator of Interferon-regulatory Factors (DAI) Promotes Lupus Nephritis by Activating the Calcium Pathway

Zhang, Weijuan; Zhou, Qian; Xu, Wei; Cai, Yanxing; Yin, Zhinan; Gao, Xiao‐Ming; Xiong, Sidong

doi:10.1074/jbc.m113.457218

Cited by 55 publications

(53 citation statements)

References 72 publications

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“…Emerging evidence indicates that signal transduction pathways mediated by TLR lead to calcium fluxes within cells through calcium channel activity from calcium stores [14,39]. Therefore, the observed calcium signaling upon esDNA treatment involved in plant early perception of esDNA might be compelling evidence of the presence of a receptor system.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Self-DNA (esDNA), but Not Heterologous Plant or Insect DNA (etDNA), Induces Plasma Membrane Depolarization and Calcium Signaling in Lima Bean (Phaseolus lunatus) and Maize (Zea mays)

Barbero

Guglielmotto

Capuzzo

et al. 2016

IJMS

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Extracellular self-DNA (esDNA) is produced during cell and tissue damage or degradation and has been shown to induce significant responses in several organisms, including plants. While the inhibitory effects of esDNA have been shown in conspecific individuals, little is known on the early events involved upon plant esDNA perception. We used electrophysiology and confocal laser scanning microscopy calcium localization to evaluate the plasma membrane potential (Vm) variations and the intracellular calcium fluxes, respectively, in Lima bean (Phaseolus lunatus) and maize (Zea mays) plants exposed to esDNA and extracellular heterologous DNA (etDNA) and to etDNA from Spodoptera littoralis larvae and oral secretions. In both species, esDNA induced a significant Vm depolarization and an increased flux of calcium, whereas etDNA was unable to exert any of these early signaling events. These findings confirm the specificity of esDNA to induce plant cell responses and to trigger early signaling events that eventually lead to plant response to damage.

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Section: Discussionmentioning

confidence: 99%

Extracellular Self-DNA (esDNA), but Not Heterologous Plant or Insect DNA (etDNA), Induces Plasma Membrane Depolarization and Calcium Signaling in Lima Bean (Phaseolus lunatus) and Maize (Zea mays)

Barbero

Guglielmotto

Capuzzo

et al. 2016

IJMS

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“…To inhibit the FOXO3a expression in lupus mice, 6-week-old female BALB/c mice were randomized for injection with siFOXO3a or siControl using in vivo-jet-PEI TM (Polyplus Transfection, Strasbourg, France) every other 3 days for 6 weeks as described previously (33,35). In brief, 24 h after the initial siFOXO3a or siControl treatment, mice were immunized with ALD-DNA (50 g/mouse), UnALD-DNA (50 g/mouse), or PBS three times in 4 weeks.…”

Section: Methodsmentioning

confidence: 99%

Blunting Autoantigen-induced FOXO3a Protein Phosphorylation and Degradation Is a Novel Pathway of Glucocorticoids for the Treatment of Systemic Lupus Erythematosus

Gao

et al. 2016

Journal of Biological Chemistry

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Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease affecting multiple organs. Glucocorticoids (GCs), the potent anti-inflammatory drugs, remain as a cornerstone in the treatment for SLE; nevertheless, their clinical efficacy is compromised by the side effects of long term treatment and resistance. To improve the therapeutic efficacy of GCs in SLE, it is important to further decipher the molecular mechanisms of how GCs exert their anti-inflammatory effects. In this investigation, FOXO3a was identified as a molecule that was down-regulated in the course of SLE.

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“…Interestingly, DAI expression is induced by activated lymphocytic-derived apoptotic DNA treatment and the level of DAI is increased significantly in SLE patients and in lupus mouse models [92]. Inhibition of DAI signalling with siRNA in lupus mouse models dampens macrophage activation and ameliorates SLE symptoms, including reduced cytokine levels in sera, anti-dsDNA antibody production and IC deposition within the kidney [92].…”

Section: Sting-dependent Pathwaymentioning

confidence: 99%

Self-dsDNA in the pathogenesis of systemic lupus erythematosus

Bai

Tong

Liu

et al. 2017

Clinical and Experimental Immunology

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SummarySystemic lupus erythematosus (SLE) is a systemic and poly-aetiological autoimmune disease characterized by the production of antibodies to autologous double-stranded DNA (dsDNA) which serve as diagnostic and prognostic markers. The defective clearance of apoptotic material, together with neutrophil extracellular traps (NETs), provides abundant chromatin or self-dsDNA to trigger the production of anti-dsDNA antibodies, although the mechanisms remain to be elucidated. In SLE patients, the immune complex (IC) of dsDNA and its autoantibodies trigger the robust type I interferon (IFN-I) production through intracellular DNA sensors, which drives the adaptive immune system to break down self-tolerance. In this review, we will discuss the potential resources of self-dsDNA, the mechanisms of self-dsDNA-mediated inflammation through various DNA sensors and its functions in SLE pathogenesis.

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DNA-dependent Activator of Interferon-regulatory Factors (DAI) Promotes Lupus Nephritis by Activating the Calcium Pathway

Cited by 55 publications

References 72 publications

Extracellular Self-DNA (esDNA), but Not Heterologous Plant or Insect DNA (etDNA), Induces Plasma Membrane Depolarization and Calcium Signaling in Lima Bean (Phaseolus lunatus) and Maize (Zea mays)

Extracellular Self-DNA (esDNA), but Not Heterologous Plant or Insect DNA (etDNA), Induces Plasma Membrane Depolarization and Calcium Signaling in Lima Bean (Phaseolus lunatus) and Maize (Zea mays)

Blunting Autoantigen-induced FOXO3a Protein Phosphorylation and Degradation Is a Novel Pathway of Glucocorticoids for the Treatment of Systemic Lupus Erythematosus

Self-dsDNA in the pathogenesis of systemic lupus erythematosus

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