TGF-β Regulates Reciprocal Differentiation of CD4+CD25+Foxp3+ Regulatory T Cells and IL-17-Producing Th17 Cells from Naïve CD4+CD25 T Cells



CD4+CD25+ T cells expressing forkhead transcription factor Foxp3 are recognized as professional regulatory T cells (Tregs) and are instrumental in the induction and maintenance of immune tolerance. In addition to their development intrathymically, CD4+ CD25+Foxp3+ Tregs may also be converted extrathymically from CD4+CD25 naïve T cells through induction of Foxp3 by transforming growth factor–beta (TGF-β). Most recently, an interleukin-17 (IL-17)-producing pro-inflammatory T helper (Th) subset, designated Th17, has been identified. Unexpectedly, the differentiation of Th17 cells from CD4+CD25 naïve T cells also requires TGF-β, but in the presence of the proinflammatory cytokine interleukin-6 (IL-6). The transcription factor that programs and directs Th17 cell differentiation includes retinoic-acid-related orphan receptor-γt (RORrt), which is induced by the combined signals from both IL-6 and TGF-β engagement. This chapter attempts to highlight the discovery and development of the TGF-β reciprocal regulation of Tregs and Th17 cells.


Th17 Cell Foxp3 Expression Th17 Cell Differentiation Double Positive Experimental Autoimmune Encephalitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This research was supported by the Intramural Research Program of the NIH, National Institute for Dental and Craniofacial Research.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Mucosal Immunology Unit, OIIBNational Institute of Dental and Craniofacial Research, National Institutes of HealthBethesdaUSA

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