c-Rel is crucial for the induction of Foxp3(+) regulatory CD4(+) T cells but not T(H)17 cells

Eur J Immunol. 2010 Mar;40(3):671-6. doi: 10.1002/eji.200940260.


The NF-kappaB/Rel family member c-Rel was described to be required for the development of T(H)1 responses. However, the role of c-Rel in the differentiation of T(H)17 and regulatory CD4(+)Foxp3(+) T cells (Treg) remains obscure. Here, we show that in the absence of c-Rel, in vitro differentiation of pro-inflammatory T(H)17 cells is normal. In contrast, generation of inducible Treg (iTreg) within c-Rel-deficient CD4(+) T cells was severely hampered and correlated to reduced numbers of Foxp3(+) T cells in vivo. Mechanistically, in vitro conversion of naive CD4(+) T cells into iTreg was crucially dependent on c-Rel-mediated synthesis of endogenous IL-2. The addition of exogenous IL-2 was sufficient to rescue the development of c-Rel-deficient iTreg. Thus, c-Rel is essential for the development of Foxp3(+) Treg but not for T(H)17 cells via regulating the production of IL-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation / immunology*
  • Cell Separation
  • Flow Cytometry
  • Forkhead Transcription Factors / immunology*
  • Interleukin-17 / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-rel / immunology*
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / immunology


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-17
  • Interleukin-2
  • Proto-Oncogene Proteins c-rel