FOXP3 and Its Role in the Immune System

FOXP3 is a member of the forkhead transcription factor family. Unlike other members, it is mainly expressed in a subset of CD4(+) T-cells that play a suppressive role in the immune system. A function of FOXP3 is to suppress the function of NFAT and NF kappa B and this leads to suppression of expression of many genes including IL-2 and effector T-cell cytokines. FOXP3 acts also as a transcription activator for many genes including CD25, Cytotoxic T-Lymphocyte Antigen 4 (CTLA4), glucocorticoid-induced TNF receptor family gene (GITR) and folate receptor 4. FOXP3(+) T-cells are made in the thymus and periphery. The FOXP3(+) T-cells made in the thymus migrate to secondary lymphoid tissues and suppress antigen priming of lymphocytes. Antigen priming of naive FOXP3(+) T-cells and naive FOXP3(-) T-cells leads to generation of memory FOXP3(+) T-cells which are efficient in migration to nonlymphoid tissues. Memory FOXP3(+) T-cells are, therefore, effective in suppression of effector T-cell function, while naive FOXP3(+) T-cells are adept at suppressing the early immune responses in lymphoid tissues. Both naive and memory FOXP3(+) T-cells are required for effective maintenance of tolerance and prevention of autoimmune diseases throughout the body. Many factors such as cytokines and noncytokine factors regulate the generation of FOXP3(+) T-cells. For example, retinoic acid, produced by the dendritic cells and epithelial cells in the intestine, works together with TGF-beta 1 and promotes generation of small intestine-homing FOXP3(+) T-cells by upregulating the expression of FOXP3 and gut homing receptors. FOXP3(+) T-cells can be produced in vitro from autologous naive T-cells and, therefore, have great therapeutic potentials in treating a number of inflammatory diseases and graft rejection.