Structural aspects of the FOXP3 regulatory complex as an immunopharmacological target.

The forkhead family transcription factor FOXP3 plays a fundamental role in immune homeostasis. FOXP3 dysfunction in regulatory T cells (Tregs) contributes to multiple disease processes such as autoimmunity, tumor development, and viral infection. FOXP3 cooperates and associates with a group of other transcriptional factors, co-repressors and co-activators in Tregs to form one or more dynamic regulatory complexes. These ensembles communicate with multiple key signaling pathways to either upregulate or downregulate the expression of downstream target genes such as cytokines and cell surface receptors, which are critical for the control of normal immune responses. Although the details of the underlying mechanism by which FOXP3 operates as a transcriptional repressor or an activator is largely undefined, FOXP3(+) Tregs based cellular therapies have been studied in animal models. Our recent studies concerning the FOXP3 complex ensemble provide structural and biochemical insights into FOXP3 function of Tregs, which are essential to the development of novel immunopharmacological agents for treating human immunological disease.