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. 2008;1(3):192-202.
Epub 2008 Jun 10.

The Critical Role of TGF-beta1 in the Development of Induced Foxp3+ Regulatory T Cells

Song Guo Zheng  1
Affiliations

The Critical Role of TGF-beta1 in the Development of Induced Foxp3+ Regulatory T Cells

Song Guo Zheng. Int J Clin Exp Med. 2008.

Abstract

Foxp3+T regulatory cell (Treg) subsets play a crucial role in the maintenance of immune homeostasis against self-antigen. The lack or dysfunction of these cells is responsible for the pathogenesis and development of many autoimmune diseases. Therefore, manipulation of these cells may provide a novel therapeutic approach to treat autoimmune diseases and prevent allograft rejection during organ transplantation. In the article, we will provide current opinions concerning the classification, developmental and functional characterizations of Treg subsets. A particular emphasis will be focused on transforming cell growth factor beta (TGF-beta) and its role in the differentiation and development of induced regulatory T cells (iTregs) in the periphery. Moreover, the similarity and disparity of iTregs and naturally occurring, thymus-derived CD4+CD25+Foxp3+ regulatory T cells (nTregs) will also be discussed. While proinflammatory cytokine IL-6 can convert nTregs to IL-17-producing cells, peripheral Tregs induced by TGF-beta are resistant to this cytokine. This difference may affect the role of each in the adaptive immune response.

Keywords: Foxp3; Immunoregulation; TGF-β; Th17 cells; regulatory T cells.

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Figures

Figure 1
Figure 1
The difference between nTregs and iTregs in the Th17 conversion when stimulated with IL-6. CD4+CD25+Foxp3+ nTregs derived from thymus convert into IL-17-producing cells and decrease Foxp3 expression when stimulated with IL-6. Conversely, similarly stimulated CD4+CD25+Foxp3+ iTregs induced with IL-2 and TGF-β from CD4+CD25− in the periphery are resistant to converting of Th17 cells and they also sustain Foxp3 phenotype and suppressive function although IL-6 and TGF-β can induce the development of Th17 cells.
See this image and copyright information in PMC

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