Epigenetic Regulation of Immunity

Abstract

Immunity is a collective response to a foreign pathogen, insult, or injury by specialized cells of the body. The hallmarks of immune responses are specificity, speed, and self-regulation. During inflammation, immune cells are in a dynamic microenvironment that interacts with and complements the plasticity of immune cell phenotypes [1]. Gene regulation is the underlying key process in activation and differentiation of immune cells. For decades, work concentrated on the discovery of factors binding to specific DNA sequences and signaling networks activating those factors while overlooking the impact of chromatin structure on the regulation of transcription. Today it is accepted that chromatin structure as well as the DNA sequence significantly defines transcription, a phenomenon often referred to as epigenetic regulation. The term “epigenetics” was first used by C. H. Waddington in 1942. Although at that time he had no knowledge of the mechanisms of gene regulation, he used the term to describe the interaction of genes with their environment to create a phenotype. Robin Holliday suggested that DNA METHYLATION is a mechanism to control gene regulation, thus defining the first mechanism of epigenetic regulation. In the 1990s, the term was loosely used until 2002 when Sir Adrian Bird proposed a unifying definition. He defined epigenetics as “the study of mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence” [2]. In 2008, a consensus definition of the concept of epigenetic trait as “stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence” was formulated at a Cold Spring Harbor meeting [3], which is widely used today.