Department of Comparative Pathobiology, 725 Harrison Street, Purdue University, West Lafayette, Indiana 47907, USA.
Adv Exp Med Biol. 2009;665:17-29. doi: 10.1007/978-1-4419-1599-3_2.
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 NFkappaB and this leads to suppression ofexpression of many genes including IL-2 and effector T-cell cytokines. FOXP3 acts also as a transcription activator for many genes induding CD2S, Cytotoxic T-Lymphocyte Antigen 4 (CTLA4), glucocorticoid-induced TNF receptorfamily gene (GITR) andfolate 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-cdlls 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-beta1 and promotes generation of small intestine-homing FOXP3 T-cells by upregulating the expression ofFOXP3 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 grafi rejection.
叉头框蛋白 P3（FOXP3）是叉头框转录因子家族的成员。与其他成员不同，它主要在免疫系统中发挥抑制作用的 CD4+T 细胞亚群中表达。FOXP3 的功能之一是抑制 NFAT 和 NFkappaB 的功能，从而抑制包括 IL-2 和效应 T 细胞细胞因子在内的许多基因的表达。FOXP3 还作为许多基因的转录激活因子发挥作用，包括 CD2S、细胞毒性 T 淋巴细胞抗原 4（CTLA4）、糖皮质激素诱导的 TNF 受体家族基因（GITR）和叶酸受体 4。FOXP3+T 细胞在胸腺和外周组织中产生。在胸腺中产生的 FOXP3+T 细胞迁移到次级淋巴组织中，抑制淋巴细胞的抗原启动。幼稚 FOXP3 T 细胞和幼稚 FOXP3 T 细胞的抗原启动导致记忆 FOXP3+T 细胞的产生，其在向非淋巴组织的迁移中有效。因此，记忆 FOXP3+T 细胞有效地抑制效应 T 细胞功能，而幼稚 FOXP3 T 细胞擅长抑制淋巴组织中的早期免疫反应。幼稚和记忆 FOXP3+T 细胞均是在全身维持耐受和预防自身免疫性疾病所必需的。许多因素，如细胞因子和非细胞因子因素，调节 FOXP3+T 细胞的产生。例如，由肠道中的树突状细胞和上皮细胞产生的视黄酸与 TGF-β1 一起作用，通过上调 FOXP3 和肠道归巢受体的表达来促进小肠归巢 FOXP3+T 细胞的产生。FOXP3+T 细胞可以从自体幼稚 T 细胞在体外产生，因此在治疗多种炎症性疾病和移植物排斥方面具有巨大的治疗潜力。
