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Sci. Signal., 31 July 2012
Vol. 5, Issue 235, p. pe32
[DOI: 10.1126/scisignal.2003364]


T Cell Signaling Targets for Enhancing Regulatory or Effector Function

Fan Pan1, Huimin Fan2, Zhongmin Liu2*, and Shuiping Jiang2*

1 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
2 Shanghai East Hospital of Tongji University, Shanghai 200120, China.

Abstract: To respond to infection, resting or naïve T cells must undergo activation, clonal expansion, and differentiation into specialized functional subsets of effector T cells. However, to prevent excessive or self-destructive immune responses, regulatory T cells (Tregs) are instrumental in suppressing the activation and function of effector cells, including effector T cells. The transcription factor Forkhead box P3 (Foxp3) regulates the expression of genes involved in the development and function of Tregs. Foxp3 interacts with other transcription factors and with epigenetic elements such as histone deacetylases (HDACs) and histone acetyltransferases. Treg suppressive function can be increased by exposure to HDAC inhibitors. The individual contributions of different HDAC family members to Treg function and their respective mechanisms of action, however, remain unclear. A study showed that HDAC6, HDAC9, and Sirtuin-1 had distinct effects on Foxp3 expression and function, suggesting that selectively targeting HDACs individually or in combination may enhance Treg stability and suppressive function. Another study showed that the receptor programmed death 1 (PD-1), a well-known inhibitor of T cell activation, halted cell cycle progression in effector T cells by inhibiting the transcription of the gene encoding the substrate-recognition component (Skp2) of the ubiquitin ligase SCFSkp2. Together, these findings reveal new signaling targets for enhancing Treg or effector T cell function that may be helpful in designing future therapies, either to increase Treg suppressive function in transplantation and autoimmune diseases or to block PD-1 function, thus increasing the magnitude of antiviral or antitumor immune responses of effector T cells.

* Corresponding author. E-mail: shuiping.jiang{at} (S.J.); zhongmin_liu{at} (Z.L.)

Citation: F. Pan, H. Fan, Z. Liu, S. Jiang, T Cell Signaling Targets for Enhancing Regulatory or Effector Function. Sci. Signal. 5, pe32 (2012).

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