Critical role of Bcl11b in suppressor function of T regulatory cells and prevention of inflammatory bowel disease

J Exp Med. 2011 Sep 26;208(10):2069-81. doi: 10.1084/jem.20102683. Epub 2011 Aug 29.


Dysregulated CD4(+) T cell responses and alterations in T regulatory cells (T(reg) cells) play a critical role in autoimmune diseases, including inflammatory bowel disease (IBD). The current study demonstrates that removal of Bcl11b at the double-positive stage of T cell development or only in T(reg) cells causes IBD because of proinflammatory cytokine-producing CD4(+) T cells infiltrating the colon. Provision of WT T(reg) cells prevented IBD, demonstrating that alterations in T(reg) cells are responsible for the disease. Furthermore, Bcl11b-deficient T(reg) cells had reduced suppressor activity with altered gene expression profiles, including reduced expression of the genes encoding Foxp3 and IL-10, and up-regulation of genes encoding proinflammatory cytokines. Additionally, the absence of Bcl11b altered the induction of Foxp3 expression and reduced the generation of induced T(reg) cells (iT(reg) cells) after Tgf-β treatment of conventional CD4(+) T cells. Bcl11b bound to Foxp3 and IL-10 promoters, as well as to critical conserved noncoding sequences within the Foxp3 and IL-10 loci, and mutating the Bcl11b binding site in the Foxp3 promoter reduced expression of a luciferase reporter gene. These experiments demonstrate that Bcl11b is indispensable for T(reg) suppressor function and for maintenance of optimal Foxp3 and IL-10 gene expression, as well as for the induction of Foxp3 expression in conventional CD4(+) T cells in response to Tgf-β and generation of iT(reg) cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Colon / cytology
  • Colon / immunology
  • Colon / pathology
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / pathology
  • Inflammatory Bowel Diseases / physiopathology
  • Inflammatory Bowel Diseases / prevention & control*
  • Integrins / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, CCR / immunology
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / immunology*


  • Bcl11b protein, mouse
  • CC chemokine receptor 9
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Integrins
  • Receptors, CCR
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • integrin alpha4beta7
  • Interleukin-10