Epigenetic Regulation

Each cell has a specific epigenome based on the same individual genome, i.e., a specific epigenetic marks (or signatures) combination. The epigenome is simultaneously stable and changeable depending on the dynamics of cell microenvironmental conditions. Some DNA regions have epigenetic marks susceptible to such factors as stress, medications, circadian rhythms, diet, and aging, impacting the epigenotype and even phenotype. Therefore, despite gene mutations' absence, epigenetic modifications and alterations can cause many diseases, especially aging-related diseases and secondary immunocompromised conditions.

The main epigenetic modifications are:

  - DNA methylation;
  - posttranslational histone modifications;
  - micro-RNA-mediated gene silencing.

Innate immunity involves the recognition of non-variable infectious components, such as pathogen-associated molecular patterns (PAMP), but adaptive immune responses rely on a highly diverse antigen-recognizing receptor repertoire generated through the rearrangement of TCR and BCR genes in T cells and B cells.

Lymphocyte function is closely associated with the processes of cell division, such as a clonal expansion, whereas the fate of daughter cells may be different from a parent cell. It is probably achieved by epigenetic modifications, which allow dividing cells to memorize signaling events in their earlier development when gene alterations are unavailable.

Identified levels of epigenetic regulations of immune responses:

  - expression of HLA molecules in antigen processing;
  - differentiation of helper T cells and effector T cells (e.g., DNA hypermethylated in naïve T cells becomes DNA demethylated in Th1 and effector T cells);
  - differentiation of FoxP3+ Treg cells (FoxP3 locus demethylation and histone hyperacetylation maintain the stable FoxP3 expression);
  - synthesis of a selected set of cytokines;
  - activation of naïve B cells (e.g., a key enzyme cytidine deaminase (AID) gene hypermethylated in naïve B cells becomes demethylated in activated B cells ready to differentiate into plasma cells).