Epigenetic modifications of the immune system in health and disease

Abstract

Vertebrate animals have developed sophisticated host defense mechanisms against potentially hostile antigens. These mechanisms mainly involve the immune system and the epithelial cells that cover the body surface. Accumulating studies have revealed that epigenetic mechanisms in collaboration with signal transduction networks regulate gene expression over the course of differentiation, proliferation and function of immune and epithelial cells. The epigenetic status of these cells is fine-tuned under physiological conditions; however, its disturbance often results in the development of immunological disorders, namely inflammation. Certain environmental factors influence the differentiation and function of immune cells through epigenetic alterations. For example, commensal microbiota-derived metabolites inhibit histone deacetylases to induce regulatory T cells, whereas some infectious agents induce DNA methylation, resulting in the development of cancer. These data imply that epigenetic regulation of host defense cells, which are usually the first to encounter external antigens, is implicated in disease development. Here, we highlight recent advances in our understanding of the molecular mechanisms by which the epigenetic status of immune and epithelial cells is controlled.

Comparison of Human Neonatal and Adult Blood Leukocyte Subset Composition Phenotypes

“…This possibility is supported, albeit somewhat controversially, in previous work [4–6,9,10] and would be interesting to explore further.…”

“…Such population-level-variation in immune phenotypes plausibly maintains plasticity in response to varying environmental pathogenic challenges and may help in adaptation to newly emerging pathogenic threats[3]. Diversity in the phenotypes of leukocyte proportions and concentrations in blood is thought to have variable contributions from genetic[4,5], environmental[6–8] and epigenetic[9–11] factors. There is evidence that socio-geographic differences have consequence in immune phenotype and function[12–15].…”

Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice

“…Self-healing of primary infections of P. chabaudi bloodstage malaria generates long-lasting immunity, which manifests itself as much lower parasitemias upon homologous rechallenge in comparison to the corresponding primary infections Wunderlich et al 2014). There is ample evidence that also genes involved in both innate and adaptive immunity are under complex epigenetic control including modifications of DNA methylation (Lim et al 2010;Rodriguez-Cortez et al 2011;Kondilis-Mangum and Wade 2013;Obata et al 2015;Hennessy and McKernan 2016). Insofar, it is rather surprising that protective vaccination and P. chabaudi infections induce changes in the DNA methylation of promoters of so many genes, most of them are related to regulation of transcription, but only very few genes can be related to any functions of the immune system inherent to the liver by gene set enrichment analyses.…”

Understanding the pathogenesis of abdominal aortic aneurysms

“…In the face of the potential relationship between cigarette smoking, AAA formation and DNA methylation [101], it is surprising that only one study has been published about the direct role of DNA methylation in AAA [102]. This study analyzed genome-wide DNA methylation profiles of patients with AAA using peripheral blood mononuclear cells, which have been used for methylation studies in other inflammatory disorders [103]. Using isolated human mononuclear blood cells and controlling for smoking status, significant differences in DNA methylation at specific CpG islands that mapped to two genes were identified: CNN2 and SERPINB9 [102].…”