Advances in T Cell Immunity: How the Environment Talks to the Genome through Epigenetics

Dear Colleagues,

Epigenetic modifications are active processes that connect genetic and environmental factors. They include DNA methylation, histone post-translational changes, and non-coding RNAs that alter chromatin conformation, controlling constitutive or inducible gene transcription without affecting gene sequences. This plays a key role in harnessing the transcriptional programs of both adaptive and innate immune cells, driving myeloid and lymphoid cell fate. Transcriptional and epigenetic reprogramming provides an augmented response of innate immune cells to a secondary challenge, a phenomenon known as “trained immunity”. Similarly, “epigenetic memory”, defined as maintenance of T-cell-specific epigenetic traits, controls cell differentiation and functional capacity following recurring antigenic exposure in memory T cells. In recent years, growing evidence supports the notion that energy metabolites modulate immune cell fate and function via epigenetic modifications. Moreover, changes in intracellular metabolism couple with activation of immune pathways and epigenetic remodeling to finetune the balance between immune cell activation and tolerance, thus regulating physiological responses to extracellular stimuli. The novel concept that chromatin represents a “key consumer” in the metabolite economy, converging metabolic status and nutrient signals to specific epigenetic outputs, represents an intriguing opportunity to control immune homeostasis and tolerance. As epigenetic and metabolic dysregulation are both distinctive characteristics of immune-related disorders, ranging from immunodeficiency to autoimmunity and cancer, this metabolism–chromatin axis may open the way for the identification of novel therapeutic targets. Indeed, several epigenetic drugs (epidrugs), affecting histone- or DNA-modifying enzymes, are now under investigation as promising therapeutic tools in autoimmunity and cancer. The challenge now is to understand how metabolic pathways, transcription factors, and chromatin components cooperate to translate extracellular stimuli into a determinant of immune cell fate choice. This Special Issue aims to provide an update on research decoding the role of epigenetics, both in health- and immune-related disorders.

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• epigenetics
• innate immunity
• adaptive immunity
• epigenetic memory
• metabolism
• epigenetic drugs
• immune tolerance
• autoimmunity
• immunodeficiency
• cancer