Inhibition of CDK2 promotes inducible regulatory T-cell differentiation through TGFβ-Smad3 signaling pathway

  • Cell Immunol. 2014 Jul;290(1):138-44. doi: 10.1016/j.cellimm.2014.05.004.
Haijuan Gu  1 ,  Lixia Ding  1 ,  Si-Dong Xiong  1 ,  Xiao-Ming Gao  2 ,  Biao Zheng  3
Affiliations
  • 1. Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China.
  • 2. Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China. Electronic address: [email protected].
  • 3. Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: [email protected].
PMID: 24978614 DOI: 10.1016/j.cellimm.2014.05.004
Abstract

Inducible regulatory T-cells (iTReg) can be generated from CD4(+)Foxp3(-) naïve conventional T-cells by a combination of TGF-β and T-cell receptor (TCR) signaling. It is of enormous clinical importance to identify agents that can promote the generation and differentiation of functional iTreg cells. We have established a phenotypic screening platform to identify new compounds that can promote the TGFβ-mediated iTreg differentiation. We have found Kenpaullone, a potent CDK1, CDK2 and CDK5 Inhibitor, as new enhancer for iTreg cell differentiation. Kenpaullone promotes iTreg cell differentiation through increased and prolonged transcription of foxp3 gene by enhancing TGFβ-Smad3 signaling pathway. Thus, we have demonstrated that CDK2 is the biological target of Kenpaullone and proven that CDK2 is a novel negative regulator of iTreg cell differentiation.

Keywords
Foxp3; Phenotypic screening; Regulatory T cells.
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