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Review
. 2013 Mar;5(3):281-9.
doi: 10.4155/fmc.12.215.

Potential of targeting TGF-β for organ transplant patients

Makio Iwashima  1 , Robert Love
Affiliations
Review

Potential of targeting TGF-β for organ transplant patients

Makio Iwashima et al. Future Med Chem. 2013 Mar.

Abstract

TGF-β was originally considered as an immunoregulatory cytokine, but accumulating data demonstrate that it also plays a critical role in development of effector immunity. Since TGF- β has a potent ability to alter immune responses, modulation of the TGF-β pathway for treatment of transplantation patients could be effective if carried out in a target selective manner. This review will focus on the role of TGF-β in T cell differentiation and discuss the prospect of TGF-β as the therapeutic target of lung transplantation acceptance.

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Conflict of interest statement

Financial & competing interests disclosure

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1
Figure 1. Effect of TGF-β on p53-induced CD28-dependent T cell apoptosis
When naive CD4 T cells are stimulated by plate-bound anti-CD3/anti-CD28 antibodies to induce apoptosis, the presence of TGF-β inhibits apoptosis. If IL-4 is present, naive CD4 T cells differentiate into Th9 cells, while presence of IL-6 promotes development of Th17 cells.
Figure 2
Figure 2. Transcriptional control of naive T cell differentiation by TGF-β and other cytokines
In naive CD4 T cells activated by antigens, TGF-β and IL-2 promote the expression of Foxp3, an essential transcription factor for iTregs development. When IL-6 is present along with TGF-β, pro-inflammatory IL-17 production is induced via activation of RORγt and STAT3. The combination of TGF-β with IL-4 leads to the expression of IL-9 by SMAD complex and STAT6.
Figure 3
Figure 3. Summary of TGF-β effect on CD4 T cells
TGF-β has both immunoregulatory and immunogenic effect on CD4 T cells. In the regulatory wing, TGF-β can directly suppress Th0 activation and block cytokine production while promoting the development of inducible Tregs. In the effector wing, TGF-β can promote the differentiation of Th9 and Th17 cells. For transplantation, it is essential to develop the method to enhance the immunoregulatory functions of TGF-β while blocking immunogenic effect. Treg: Regulatory T cell.
See this image and copyright information in PMC

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