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FOXP3 and Its Role in the Immune System

  • Chapter
Forkhead Transcription Factors

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 665))

Abstract

FOXP3 is a member of the forkhead transcription factor family. Unlike other members, it is mainly expressed in a subset ofCD4+ T-cells that play a suppressive role in the immune system. A function of FOXP3 is to suppress the function of NFAT and NFKB 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 Antigen4 (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 naïve FOXP3+ T-cells and naïve 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 naïve 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-β1 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 naïve T-cells and, therefore, have great therapeutic potentials in treating a number of inflammatory diseases and graft rejection.

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Authors and Affiliations

  1. Laboratory of Immunology and Hematopoiesis Department of Comparative Pathobiology Purdue Cancer Center, Purdue University, West Lafayette, Indiana, USA

    Chang H. Kim

  2. Department of Comparative Pathobiology, Purdue University, 725 Harrison Street, West Lafayette, Indiana, 47907, USA

    Chang H. Kim

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  1. Chang H. Kim
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Editors and Affiliations

  1. Division of Cellular and Molecular Cerebral Ischemia, Wayne State University School of Medicine, Detroit, Michigan, USA

    Kenneth Maiese MD

  2. Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan, USA

    Kenneth Maiese MD

  3. Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, USA

    Kenneth Maiese MD

  4. Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA

    Kenneth Maiese MD

  5. Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USA

    Kenneth Maiese MD

  6. Institute of Environmental Health Sciences, Wayne State University School of Medicine, Detroit, Michigan, USA

    Kenneth Maiese MD

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Kim, C.H. (2009). FOXP3 and Its Role in the Immune System. In: Maiese, K. (eds) Forkhead Transcription Factors. Advances in Experimental Medicine and Biology, vol 665. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1599-3_2

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