Epigenetic Regulation of T-Helper Cell Differentiation

CD4+ T helper (Th) cells are part of the adaptive immune system and are responsible for activating other immune cells, such as B cells, CD8+ T cells, macrophages, mast cells, neutrophils, eosinophils, and ba- sophils. Differentiation of CD4+ T cells is under the impression of cytokines and stimulation of the T cell receptor by different antigens. The pattern of cytokine secretion can be altered under specific conditions from one cell line to another, indicating that Th cells have plasticity. In fact, active and master regulators collaborate with transcription factors like signal transducers, activator transducer transducers, activator transducers, and activator transducers and activators of transcriptions (STATs) in developing the differen- tiation process. The signals provided by cytokines activate specific transcription factors in each cell line. During this process, epigenetic modifications are actively involved. Epigenetics is defined as heritable alterations in the regulation of gene expression without any change in the DNA strand and includes DNA methylation, histone modification, and non-coding RNAs. The plasticity of CD4+ T cells in differentiation to multiple subsets allows Th cells to exhibit the best immune response possible against the target micro- organism. Failure to respond appropriately to multiple types of microorganisms can lead to disease. In this review, we have collected recent advances in understanding the role of epigenetic regulatory mechanisms in the differentiation of Th cells and, thereby, the commitment of CD4+ T cells to a particular lineage to raise an appropriate response against a variety of microorganisms.