Epigenetics: An opportunity to shape innate and adaptive immune responses

Epigenetics connects genetic and environmental factors: it includes DNA methyl-ation, histone post-translational modifications and the regulation of chromatinaccessibility by non-coding RNAs, all of which control constitutive or induciblegene transcription. This plays a key role in harnessing the transcriptional pro-grams of both innate and adaptive immune cells due to its plasticity andenvironmental-driven nature, piloting myeloid and lymphoid cell fate decisionswith no change in their genomic sequence. In particular, epigenetic marks at thesite of lineage-specific transcription factors and maintenance of cell type-specificepigenetic modifications, referred to as‘epigenetic memory’, dictate cell differen-tiation, cytokine production and functional capacity following repeated antigenicexposure in memory T cells. Moreover, metabolic and epigenetic reprogrammingoccurring during a primary innate immune response leads to enhanced responsesto secondary challenges, a phenomenon known as‘trained immunity’. Here, we discuss how stable and dynamic epigenetic states control immune cell identityand plasticity in physiological and pathological conditions. Dissecting the regula-tory circuits of cell fate determination and maintenance is of paramount impor-tance for understanding the delicate balance between immune cell activation andtolerance, in healthy conditions and in autoimmune diseases.