Immune cell development and activation demand the precise and coordinated control of transcriptional programmes. Three-dimensional (3D) organization of the genome has emerged as an important regulator of chromatin state, transcriptional activity and cell identity by facilitating or impeding long-range genomic interactions among regulatory elements and genes. Chromatin folding thus enables cell type-specific and stimulus-specific transcriptional responses to extracellular signals, which are essential for the control of immune cell fate, for inflammatory responses and for generating a diverse repertoire of antigen receptor specificities. Here, we review recent findings connecting 3D genome organization to the control of immune cell differentiation and function, and discuss how alterations in genome folding may lead to immune dysfunction and malignancy.
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