Loss of epigenetic modifications on the inactive X chromosome and sex-biased gene expression profiles in B cells from NZB/W F1 mice with lupus-like disease
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE140277 | GEO | 2019/11/13
REPOSITORIES: GEO
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Project description:Transcriptomic analysis of gene expression of splenocytes from 16-week-old female NZB/NZW F1 (BWF1) mice, which are prone to lupus, and comparison to gene expression of splenocytes from male BWF1 and female BALB/c mice, which are not prone to lupus. Results provide insight into the differences in immunological activities that make female BWF1 mice more susceptible to lupus.
2021-04-01 | GSE167273 | GEO
Project description:NZB/WF1 female mice spontaneously develop autoimmune lupus nephritis. Expression profiling of kidney tissue from (a) 12 week NZB/W F1 female mice defined as asymptomatic for lupus nephritis, (b) 36 and 42 week NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 and 42 week NZB/W F1 female mice that are diseased/symptomatic for lupus nephritis and treated with Sirolimus was carried out. The goal of the study was to identify genes associated with lupus nephritis and modulated by Sirolimus, an inhibitor of mTOR. In addition, lupus nephritis genes resistant to Sirolimus therapy were also identfied
2008-11-21 | GSE12024 | GEO
Project description:NZB/WF1 female mice spontaneously develop autoimmune lupus nephritis. Expression profiling of kidney tissue from (a) 12 week NZB/W F1 female mice defined as asymptomatic for lupus nephritis, (b) 36 and 42 week NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 and 42 week NZB/W F1 female mice that are diseased/symptomatic for lupus nephritis and treated with Sirolimus was carried out. The goal of the study was to identify genes associated with lupus nephritis and modulated by Sirolimus, an inhibitor of mTOR. In addition, lupus nephritis genes resistant to Sirolimus therapy were also identfied This series of samples comprises of kidney tissue from (a) 12 week old NZB/W F1 female mice defined as asymptomatic for lupus nephritis (N=4), (b) 36 (N=3) and 42 week (N=3) old NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 (N=3)and 42 (N=3) week old NZB/W F1 female mice that are asymptomatic for lupus nephritis on treatment with Sirolimus
2008-11-20 | E-GEOD-12024 | biostudies-arrayexpress
Project description:Lupus nephritis with pronounced signs of chronic kidney disease leads to significant changes in the heart. It is not yet clear whether these changes are caused by the chronic kidney disease or by the autoimmune disease. It is also unclear which factors are responsible for the cardiovascular changes. Therefore, the gene expression of mice with lupus nephritis (NZB_W) will be compared with healthy controls (NZW).
2024-02-16 | GSE226308 | GEO
Project description:The mechanisms underlying the female-bias in autoimmunity are poorly understood. The contribution of genetic and epigenetic factors from the inactive X chromosome (Xi) are beginning to emerge as critical mediators of autoimmunity in females. Here, we ask how epigenetic features of the Xi change during disease development in B cells from the NZB/W F1 spontaneous mouse model of lupus, which is female-biased. We find that Xist RNA becomes increasingly mislocalized from the Xi with disease onset. While NZB/W F1 naïve B cells have H3K27me3 foci on the Xi, which are missing from healthy C57BL/6 and BALB/c mice, these foci are progressively lost in stimulated B cells during disease. Using single-molecule RNA FISH, we show that the X-linked gene Tlr7 is biallelically expressed in ~20% of NZB/W F1 B cells, and that the amount of biallelic expression does not change with disease. We also present sex-specific gene expression profiles for diseased NZB/W F1 B cells, and find female-specific upregulation of 20 genes, including the autoimmunity-related genes Cxcl13, Msr1, Igj, and Prdm1. Together, these studies provide important insight into the loss of epigenetic modifications from the Xi and changes with gene expression in a mouse model of female-biased SLE.
| S-EPMC7237307 | biostudies-literature
Project description:Systemic lupus erythematosous (SLE) is an autoimmune disease with an important clinical and biological heterogeneity. B lymphocytes appear central to the development of SLE which is characterized by the production of a large variety of autoantibodies and hypergammaglobulinemia. In mice, immature B cells from spontaneous lupus prone animals are able to produce autoantibodies when transferred into immunodeficient mice, strongly suggesting the existence of intrinsic B cell defects during lupus. In order to approach these defects in humans, we compared the peripheral B cell transcriptomes of quiescent lupus patients to normal B cell transcriptomes. 17 patients with quiescent lupus (patient1-17) versus 9 controls (Control1-6,Control8-10).
2011-06-23 | E-GEOD-30153 | biostudies-arrayexpress
Project description:Systemic lupus erythematosous (SLE) is an autoimmune disease with an important clinical and biological heterogeneity. B lymphocytes appear central to the development of SLE which is characterized by the production of a large variety of autoantibodies and hypergammaglobulinemia. In mice, immature B cells from spontaneous lupus prone animals are able to produce autoantibodies when transferred into immunodeficient mice, strongly suggesting the existence of intrinsic B cell defects during lupus. In order to approach these defects in humans, we compared the peripheral B cell transcriptomes of quiescent lupus patients to normal B cell transcriptomes.
2011-06-23 | GSE30153 | GEO
Project description:Glomerulonephritis is one of the major complications and causes of death in systemic lupus erythematosus (SLE). Podocytes can be injured in many forms of glomerular disease, characteristic changes are actin cytoskeleton reorganization of involved foot process. ACTN4, encodes α-actinin-4, an actin-binding and crosslinking protein localized to podocytes in renal glomerulus. Abnormal expression of α-actinin-4 in mice leads to proteinuria and podocyte damage. DZ2002, a reversible S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor with immunosuppressive properties and potent therapeutic activity against various autoimmune diseases in mice. Here, we found that DZ2002 could significantly ameliorate nephritis of lupus-prone mice. Our results showed that DZ2002 decreased the accumulation of α-actinin-4, inhibited expression of integrin-linked kinase and downstream phosphorylation of β1-integrin.
2019-11-12 | PXD010059 | Pride
Project description:As a key anti-inflammatory cytokine, IL-10 is crucial in preventing inflammatory and autoimmune diseases. However, in human and murine lupus, its role remains controversial. Our aim was to understand regulation and immunologic effects of IL-10 on different immune functions in the setting of lupus. This was explored in lupus-prone NZB/W F1 mice in vitro and vivo to understand IL-10 effects on individual immune cells as well as in the complex in vivo setting. We found pleiotropic IL-10 expression that largely increased with progressing lupus, while IL-10 receptor (IL-10R) levels remained relatively stable. In vitro experiments revealed pro- and anti-inflammatory IL-10 effects. Particularly, IL-10 decreased pro-inflammatory cytokines and slowed B cell proliferation, thereby triggering plasma cell differentiation. The frequent co-expression of ICOS, IL-21 and cMAF suggests that IL-10-producing CD4 T cells are important B cell helpers in this context. In vitro and in vivo effects of IL-10 were not fully concordant. In vivo IL-10R blockade slightly accelerated clinical lupus manifestations and immune dysregulation. Altogether, our side-by-side in vitro and in vivo comparison of the influence of IL-10 on different aspects of immunity shows that IL-10 has dual effects. Our results further reveal that the overall outcome may depend on the interplay of different factors such as target cell, inflammatory and stimulatory microenvironment, disease model and state. A comprehensive understanding of such influences is important to exploit IL-10 as a therapeutic target.
| S-EPMC7866297 | biostudies-literature
Project description:BackgroundPatients with systemic lupus erythematosus (SLE), an autoimmune disease, have a higher risk of cardiovascular (CV) disease and death. In addition, up to 40%-50% of SLE patients develop lupus nephritis (LN) and chronic kidney disease, which is an additional CV risk factor. Thus, the individual contributions of LN and other SLE-specific factors to CV events are unclear.MethodsIn this study, we investigated the effect of LN on the development of CV changes using the female NZBxNZW F1 (NZB/W) mouse model of lupus-like disease, with female NZW mice as controls. Standard serologic, morphologic, immunohistologic, and molecular analyses were performed. In a separate group of NZB/W mice, systolic blood pressure (BP) was measured during the course of the disease using tail plethysmography.ResultsOur data show marked CV changes in NZB/W mice, i.e., increased heart weight, hypertrophy of the left ventricle (LV) and septum, and increased wall thickness of the intramyocardial arteries and the aorta, which correlated with the progression of renal damage, but not with the age of the mice. In addition, systolic BP was increased in NZB/W mice only when kidney damage progressed and proteinuria was present. Pathway analysis based on gene expression data revealed a significant upregulation of the response to interferon beta in NZB/W mice with moderate kidney injury compared with NZB mice. Furthermore, IFI202b and IL-6 mRNA expression is correlated with CV changes. Multiple linear regression analysis demonstrated serum urea as a surrogate marker of kidney function and IFI202b expression as an independent predictor for LV wall thickness. In addition, deposition of complement factors CFD and C3c in hearts from NZB/W mice was seen, which correlated with the severity of kidney disease.ConclusionsThus, we postulate that the pathogenesis of CV disease in SLE is affected by renal impairment, i.e., LN, but it can also be partly influenced by lupus-specific cardiac expression of pro-inflammatory factors and complement deposition.
| S-EPMC10405627 | biostudies-literature