The study of interactions between genome and exposome in the development of systemic lupus erythematosus

Leffers, Henrik Christian Bidstrup; Lange, Theis; Collins, Christopher; Ulff-Møller, Constance J.; Jacobsen, Søren

doi:10.1016/j.autrev.2018.11.005

Cited by 52 publications

(26 citation statements)

References 105 publications

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“…The impact of exposome effect on chronic disease was quantified in 2016 by Rapoport, 8 , who estimated the effect to 80%, while the genome-wide-associated diseases did not exceed 20%. 9 Our microbiota, a collection of micro-organisms, is a living ecosystem both inside (gut) and outside (skin) of our body. Typically located at the interface of our inner and outer barrier of the body, where its main role is to maintain health.…”

Section: Introductionmentioning

confidence: 99%

The Skin Interactome: A Holistic “Genome-Microbiome-Exposome” Approach to Understand and Modulate Skin Health and Aging

Khmaladze¹,

Leonardi²,

Fabre³

et al. 2020

CCID

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Higher demands on skin care cosmetic products for strong performance drive intense research to understand the mechanisms of skin aging and design strategies to improve overall skin health. Today we know that our needs and influencers of skin health and skin aging change throughout our life journey due to both extrinsic factors, such as environmental factors and lifestyle factors, as well as our intrinsic factors. Furthermore, we need to consider our microflora, a collection of micro-organisms such as bacteria, viruses, and fungi, which is a living ecosystem in our gut and on our skin, that can have a major impact on our health. Here, we are viewing a holistic approach to understand the collective effect of the key influencers of skin health and skin aging both reviewing how each of them impact the skin, but more importantly to identify molecular conjunction pathways of these different factors in order to get a better understanding of the integrated “genome-microbiome-exposome” effect. For this purpose and in order to translate molecularly the impact of the key influencers of skin health and skin aging, we built a digital model based on system biology using different bioinformatics tools. This model is considering both the positive and negative impact of our genome (genes, age/gender), exposome: external (sun, pollution, climate) and lifestyle factors (sleep, stress, exercise, nutrition, skin care routine), as well as the role of our skin microbiome, and allowed us in a first application to evaluate the effect of the genome in the synthesis of collagen in the skin and the determination of a suitable target for boosting pro-collagen synthesis. In conclusion, we have, through our digital holistic approach, defined the skin interactome concept, as an advanced tool to better understand the molecular genesis of skin aging and further develop a strategy to balance the influence of the exposome and microbiome to protect, prevent, and delay the appearance of skin aging signs and preserve good skin health condition. In addition, this model will aid in identifying and optimizing skin treatment options based on external triggers, as well as helping to design optimal treatments modulating the intrinsic pathways.

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Section: Introductionmentioning

confidence: 99%

The Skin Interactome: A Holistic “Genome-Microbiome-Exposome” Approach to Understand and Modulate Skin Health and Aging

Khmaladze¹,

Leonardi²,

Fabre³

et al. 2020

CCID

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“…Development of lupus depends on genetic pre-disposition, but the initiation and progression of autoimmunity can be positively or negatively influenced by environmental factors ( 10 ). One environmental factor that has been epidemiologically associated with lupus and other autoimmune diseases is crystalline silica (cSiO 2 ), a respirable particle frequently inhaled by workers in occupations such as mining, construction, and farming ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Omega-3 Docosahexaenoic Acid (DHA) Impedes Silica-Induced Macrophage Corpse Accumulation by Attenuating Cell Death and Potentiating Efferocytosis

et al. 2020

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Airway exposure of lupus-prone NZBWF1 mice to crystalline silica (cSiO 2 ), a known trigger of human autoimmune disease, elicits sterile inflammation and alveolar macrophage death in the lung that, in turn, induces early autoimmune onset and accelerates lupus progression to fatal glomerulonephritis. Dietary supplementation with docosahexaenoic acid (DHA), a marine ω-3 polyunsaturated fatty acid (PUFA), markedly ameliorates cSiO 2 -triggered pulmonary, systemic, and renal manifestations of lupus. Here, we tested the hypothesis that DHA influences both cSiO 2 -induced death and efferocytotic clearance of resultant cell corpses using three murine macrophage models: (i) primary alveolar macrophages (AM) isolated from NZBWF1 mice; (ii) self-renewing AM-like Max Planck Institute (MPI) cells isolated from fetuses of C57BL/6 mice, and (iii) RAW 264.7 murine macrophages, a virus-transformed cell line derived from BALB/c mice stably transfected with the inflammasome adaptor protein ASC (RAW-ASC). Incubation with cSiO 2 at 25 and 50 μg/ml for 6 h was found to dose-dependently induce cell death ( p < 0.05) in all three models as determined by both acridine orange/propidium iodide staining and release of lactate dehydrogenase into cell culture supernatant. Pre-incubation with DHA at a physiologically relevant concentration (25 μM) significantly reduced cSiO 2 -induced death ( p < 0.05) in all three models. Cell death induction by cSiO 2 alone and its suppression by DHA were primarily associated with caspase-3/7 activation, suggestive of apoptosis, in AM, MPI, and RAW-ASC cells. Fluorescence microscopy revealed that all three macrophage models were similarly capable of efferocytosing RAW-ASC target cell corpses. Furthermore, MPI effector cells could likewise engulf RAW-ASC target cell corpses elicited by treatment with staurosporine (apoptosis), LPS, and nigericin (pyroptosis), or cSiO 2 . Pre-incubation of RAW-ASC target cells with 25 μM DHA prior to death induced by these agents significantly enhanced their efferocytosis ( p < 0.05) by MPI effector cells. In contrast, pre-incubating MPI effector cells with DHA did not affect engulfment of RAW-ASC target cells pre-incubated with vehicle. Taken together, these findings indicate that DHA at a physiologically relevant concentration was capable of attenuating macrophage death and could potentiate efferocytosis, with the net effect of reducing accumulation of cell corpses capable of eliciting autoimmunity.

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“…Introduction Systemic lupus erythematosus (SLE) is a complex, chronic, potentially fatal, multisystem autoimmune disease, which predominantly affects women between puberty and menopause [1]. The major pathogenetic mechanisms of SLE include an inappropriate immune response to the nucleic acid containing cellular particles, which is caused by an autoimmune reaction of the innate and adaptive immune systems, leading to damage structures of the skin, joints, kidney and central nervous system [2,3].…”

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confidence: 99%

Diagnostic significance of circulating miRNAs in systemic lupus erythematosus

et al. 2019

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BackgroundIn recent years, many studies focused on the association between the microRNAs (miR-NAs) and the risk of systemic lupus erythematosus (SLE), especially miRNA-21 (miR-21). We aimed to investigate the role of circulating miRNAs, especially the miR-21, as a biomarker in detecting SLE. MethodsWe searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure through Mar 3th, 2019. We performed this metaanalysis in a fixed/random-effect model using Meta-disc 1.4 and STATA 15.1. ResultsA total of 17 relevant studies were eligible to analyze pooled accuracy. The overall performance of total mixed miRNAs (TmiRs) detection was: pooled sensitivity, 0.71 (95% confidence interval [CI], 0.69 to 0.72); pooled specificity, 0.81 (95%CI, 0.79 to 0.83); and area under the summary receiver operating characteristic curves value (SROC), 0.8797. The miR-21 detection was: pooled sensitivity, 0.68 (95%CI, 0.62 to 0.74); pooled specificity, 0.77 (95%CI, 0.69 to 0.84); and SROC, 0.8281. The meta-regression analysis showed that the type of samples was the sources of heterogeneity. The subgroup analysis suggested that detection in plasma group had the largest AUC of SROC in all the subgroups: pooled sensitivity, 0.8 (95%CI, 0.78 to 0.82); pooled specificity, 0.83 (95%CI, 0.8 to 0.86); and SROC, 0.9068. ConclusionsOur meta-analysis demonstrated that circulating miRNAs might be potential novel biomarkers for detecting SLE, especially miR-21. Moreover, plasma is recommended as the clinical specimen for diagnostic detection.

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The study of interactions between genome and exposome in the development of systemic lupus erythematosus

Cited by 52 publications

References 105 publications

The Skin Interactome: A Holistic “Genome-Microbiome-Exposome” Approach to Understand and Modulate Skin Health and Aging

The Skin Interactome: A Holistic “Genome-Microbiome-Exposome” Approach to Understand and Modulate Skin Health and Aging

Omega-3 Docosahexaenoic Acid (DHA) Impedes Silica-Induced Macrophage Corpse Accumulation by Attenuating Cell Death and Potentiating Efferocytosis

Diagnostic significance of circulating miRNAs in systemic lupus erythematosus

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