Targeting Nuclear Receptors for T17-Mediated Inflammation: REV-ERBerations of Circadian Rhythm and Metabolism.

Since their discovery, a significant amount of progress has been made understanding T helper 17 (T17) 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 T17 cell development, clearance of infections, and disease. The nuclear receptor RORγt has been identified as a key regulator of T17-mediated inflammation.

High throughput screening for compounds to the orphan nuclear receptor NR2F6.

NR2F6 is considered an orphan nuclear receptor since its endogenous ligand has yet to be identified. Recently, NR2F6 has emerged as a novel cancer therapeutic target. NR2F6 has been demonstrated to be upregulated or overexpressed in several cancers.

A Compass to Guide Insights into T17 Cellular Metabolism and Autoimmunity.

T cells rapidly convert their cellular metabolic requirements upon activation, switching to a highly glycolytic program to satisfy their increasingly complex energy needs. Fundamental metabolic differences have been established for the development of Foxp3 T regulatory (Treg) cells versus T17 cells, alterations of which can drive disease. T17 cell dysregulation is a driver of autoimmunity and chronic inflammation, contributing to pathogenesis in diseases such as multiple sclerosis.