Targeting Nuclear Receptors for T_H17-Mediated Inflammation: REV-ERBerations of Circadian Rhythm and Metabolism

Since their discovery, a significant amount of progress has been made understanding T helper 17 (T_H17) cells' roles in immune homeostasis and disease. Outside of classical cytokine signaling, environmental and cellular intrinsic factors, including metabolism, have proven to be critical for non-pathogenic vs pathogenic T_H17 cell development, clearance of infections, and disease. The nuclear receptor RORγt has been identified as a key regulator of T_H17-mediated inflammation. Nuclear receptors regulate a variety of physiological processes, ranging from reproduction to the circadian rhythm, immunity to metabolism. Outside of RORγt, the roles of other nuclear receptors in T_H17-mediated immunity are not as well established. In this mini-review we describe recent studies that revealed a role for a different member of the nuclear receptor superfamily, REV-ERBα, in the regulation of T_H17 cells and autoimmunity. We highlight similarities and differences between reports, potential roles beyond T_H17-mediated cytokine regulation, unresolved questions in the field, as well as the translational potential of targeting REV-ERBα.