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

Arpita Mondal, Deepali Sawant, Alexander Dent

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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-β 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-β, 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.

Original languageEnglish
Pages (from-to)4123-4132
Number of pages10
JournalJournal of Immunology
Volume184
Issue number8
DOIs
StatePublished - Apr 15 2010

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Macrophages
T-Lymphocytes
Gene Expression
Interleukin-17
Interleukin-4
Repressor Proteins
Interleukin-23
Retroviridae
Conditioned Culture Medium
Cell Differentiation
Interleukin-6
Cell Culture Techniques
Cytokines
Messenger RNA

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Transcriptional repressor BCL6 controls Th17 responses by controlling gene expression in both T cells and macrophages. / Mondal, Arpita; Sawant, Deepali; Dent, Alexander.

In: Journal of Immunology, Vol. 184, No. 8, 15.04.2010, p. 4123-4132.

Research output: Contribution to journalArticle

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