Send to:

Choose Destination
See comment in PubMed Commons below
J Immunol. 2010 Apr 15;184(8):4123-32. doi: 10.4049/jimmunol.0901242. Epub 2010 Mar 8.

Transcriptional repressor BCL6 controls Th17 responses by controlling gene expression in both T cells and macrophages.

Author information

  • 1Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.


The transcriptional repressor protein BCL6 regulates T cell differentiation by repressing Th2 responses and promoting follicular Th cell responses. However, little is known about the role of BCL6 in Th17 responses. We found that memory T cells from BCL6-deficient mice had increased IL-17 production. Additionally, BCL6 expression is upregulated in CD4 T cells cultured under Th17 conditions. T cells from BCL6-deficient mice showed defective Th17 differentiation and enhanced IL-4 production in vitro; however, normal Th17 differentiation was obtained with BCL6-deficient T cells under culture conditions when highly pure naive CD4 T cells were used, when IL-4 production was inhibited, or when TGF-beta levels were increased. Retrovirus-mediated expression of BCL6 in CD4 T cells repressed IL-4 and augmented basal IL-17 mRNA expression. These data support the idea that BCL6 promotes Th17 differentiation through suppression of Th2 differentiation. BCL6-deficient T cells transplanted into Rag1(-/-) mice produced wild-type levels of IL-17, indicating that, in vivo, BCL6-deficient T cells develop relatively normal Th17 responses. Macrophages from BCL6-deficient mice showed strikingly increased expression of the Th17-promoting cytokines IL-6, IL-23, and TGF-beta, and conditioned media from BCL6-deficient macrophages promoted augmented IL-17 expression by T cells. We propose that the increased Th17 activity in BCL6-deficient mice is due, in part, to BCL6-deficient macrophages promoting increased Th17 differentiation in vivo. T cells may require BCL6 for optimal Th17 differentiation; however, BCL6 function in macrophages critically regulates Th17 differentiation in vivo. We hypothesize that increased Th17 differentiation aggravates the severe Th2-type inflammatory disease in BCL6-deficient mice.

[PubMed - indexed for MEDLINE]
Free full text

LinkOut - more resources

Full Text Sources

Other Literature Sources

Molecular Biology Databases

Research Materials


PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk