Demethylation of TNFSF7 contributes to CD70 overexpression in CD4+ T cells from patients with systemic sclerosis

Jiang, Hong-Yan; Xiao, Rong; Lian, Xiao-ri; Kanekura, Takuro; Luo, Yangyang; Yin, YongXing; Zhang, Guiying; Yang, Yan; Wang, Yaoyao; Zhao, Ming; Lu, Qianjin

doi:10.1016/j.clim.2012.01.005

Cited by 84 publications

(46 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD70 is a costimulatory molecule that is expressed on the surface of activated lymphocytes and plays an important role in regulating B and T cell activation [43]. Jiang et al demonstrated upregulation of CD70 expression in SSc-CD4+ T cells in association with hypomethylation of CD70 promoter gene [44]. Overall, the data suggest that DNA methylation aberrancies contribute to the overexpression of this costimulatory molecule that, in turn, leads to a cascade of T cell and B cell activation and plasma cell proliferation, which may lead to a break in immune tolerance in SSc.…”

Section: Dna Methylation and Cd70/cd27 Costimulatory Axis In Ssc T Lymentioning

confidence: 99%

Epigenetics and systemic sclerosis

Altorok

Kahaleh

2015

Semin Immunopathol

View full text Add to dashboard Cite

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vascular injury, activation of the immune system, and diffuse tissue fibrosis. The precise etiology of SSc is undetermined, but there is evidence suggestive of a connection between environmental factors and SSc pathogenesis. In general, harmful environmental factors are sensed by the epigenetic regulatory mechanisms that alter host gene expression leading to the emergence of disease-specific phenotype. There are three epigenetic mechanisms involved in gene regulation: DNA methylation, histone modifications, and microRNAs. Although there is evidence that SSc phenotype could be, to a some degree, determined by genetic variants, it is clear now that non-genetic factors outweigh the genetic risk in SSc. Accordingly, the environment can trigger epigenetic regulation that in turn establishes a molecular framework linking environmental exposures to genetics, leading to the disease process, possibly in a genetically predisposed host. Although we have just begun to appreciate the potential role of epigenetics in SSc, many important and promising clues have been observed. In this review, we will summarize the work that has been done in the field of epigenetic regulation in SSc, and we will discuss possible factors and mechanisms that may lead to epigenetic dysregulation in SSc.

show abstract

Section: Dna Methylation and Cd70/cd27 Costimulatory Axis In Ssc T Lymentioning

confidence: 99%

Epigenetics and systemic sclerosis

Altorok

Kahaleh

2015

Semin Immunopathol

View full text Add to dashboard Cite

show abstract

“…With atherosclerosis there is a progression through a timeline during which the transition from acute to chronic (or unresolved) inflammation results in inflammation-driven hypertension [101]. [189][190][191] Type 1 diabetes Macrophage overproduction of inflammatory cytokines and CD4+ Th1 subpopulation driven inflammation [192] A similar relationship exists between inflammation and metabolic disorders. Osborn and Olefsky [102] argue that chronic tissue inflammation mediated by macrophages is a critical link between the immune system and metabolic-based chronic diseases.…”

Section: Misregulated Inflammation Is the Root Of Most Chronic Diseasesmentioning

confidence: 99%

The Completed Self: An Immunological View of the Human-Microbiome Superorganism and Risk of Chronic Diseases

Dietert

Dietert²

2012

Entropy

View full text Add to dashboard Cite

Abstract:In this review, we discuss an immunological-driven sign termed the Completed Self, which is related to a holistic determination of health vs. disease. This sign (human plus commensal microbiota) forms the human superorganism. The worldwide emergence of an epidemic of chronic diseases has caused increased healthcare costs, increased premature mortality and reduced quality of life for a majority of the world's population. In addition, it has raised questions concerning the interactions between humans and their environment and potential imbalances. Misregulated inflammation, a host defensehomeostasis disorder, appears to be a key biomarker connecting a majority of chronic diseases. We consider the apparent contributors to this disorder that promote a web of interlinked comorbid conditions. Three key events are suggested to play a role: (1) altered epigenetic programming (AEP) that may span multiple generations, (2) developmental immunotoxicity (DIT), and (3) failure to adequately incorporate commensal microbes as a newborn (i.e., the incomplete self). We discuss how these three events can combine to determine whether the human superorganism is able to adequately and completely form during early childhood. We also discuss how corruption of this event can affect the risk of later-life diseases.

show abstract

“…Thus, DNA methylation results in histone deacetylation leading to the transcriptional repression of target genes through chromatin condensation. In SSc, DNA hypermethylation of the FLI1 and KLF5 genes in dermal fibroblasts (Noda et al, 2014;Wang et al, 2006) and the BMPRII gene in microvascular endothelial cells (Wang and Kahaleh, 2013) and DNA hypomethylation of the ACTA2 gene in lung fibroblasts (Hu et al, 2011) and the CD40L and CD70 genes in CD4 + T cells (Jiang et al, 2012;Lian et al, 2012) have been reported (Broen et al, 2014). Also, hypoacetylation of histone H3 and H4 in the FLI1 and KLF5 promoters is exhibited in SSc dermal fibroblasts (Noda et al, 2014;Wang et al, 2006).…”

Section: Introductionmentioning

confidence: 98%

Epigenetic suppression of Fli1, a potential predisposing factor in the pathogenesis of systemic sclerosis

Asano

2015

The International Journal of Biochemistry & Cell Biology

View full text Add to dashboard Cite

Demethylation of TNFSF7 contributes to CD70 overexpression in CD4+ T cells from patients with systemic sclerosis

Cited by 84 publications

References 23 publications

Epigenetics and systemic sclerosis

Epigenetics and systemic sclerosis

The Completed Self: An Immunological View of the Human-Microbiome Superorganism and Risk of Chronic Diseases

Epigenetic suppression of Fli1, a potential predisposing factor in the pathogenesis of systemic sclerosis

Contact Info

Product

Resources

About