Nuclear Receptors and Coregulators in Metabolism and Immunity

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors (TFs). Their activation can be manipulated via specific ligands, which can be endogenous metabolites (i.e. fatty acids, steroid hormones, bile acids) and natural compounds or synthesized chemicals. NRs are involved in a plethora of physiological processes ranging from development and reproduction to homeostasis and inflammation. As a result, this family of proteins have long been considered appealing pharmaceutical targets for treating metabolic and inflammatory diseases. Despite this recognition, most of the clinically employed NR-targeting ligands have moderate to severe side effects, largely due to their wide-spectrum of transcriptional targets. Activation of NRs exerts high tissue-specific regulation in different microenvironment stimulus contexts, possibly due to different TF and coregulator profiles, the interplaying network of which remains largely unclarified. To date, the functional and mechanistic aspects of different NRs in metabolic and immune cells are still not clear enough. Ongoing and future efforts are required to achieve the true clinical potential of these receptors, which include but are not limited to: 1) The functions of NRs in different cell types (especially metabolic and immune cells) upon various micro- and macro-environmental stimulus in both physiological and pathological conditions, and their involvement in disease contexts; 2) The crosstalk between NRs and their coregulators (both corepressors and coactivators) in controlling their activity and gene selectivity in the genomic and epigenomic levels; 3) Physiological relevant post-translational modifications that define the NR interactome, cistrome and transcriptome regulation; and 4) Screening or structure-based designing of more specific NR activators or repressors (targeting either single or multiple NRs) with maximized therapeutic potential and diminished negative effects.
This research topic aims to summarize current knowledge and to report new findings in the NR area with major focus on metabolism and immunity, especially in humans. Both research articles and reviews are accepted.