Inhibition of Th2 differentiation and GATA-3 expression by BCL-6

Saritha Kusam, Lisa M. Toney, Hiroshi Sato, Alexander Dent

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

The B cell lymphoma (BCL)-6 transcriptional repressor protein is an important regulator of Th2 responses. Mice deficient in BCL-6 develop severe Th2-type inflammation that can develop even in the absence of IL-4 signaling. We have investigated the mechanism for how BCL-6 regulates Th2 cell differentiation and have found that IL-6 signaling can promote dramatically increased levels of Th2 differentiation in BCL-6-/- CD4 T cells compared with wild-type CD4 T cells. IL-6 can induce a low level of Th2 cytokine expression in BCL-6-/-STAT6-/- cells but not in STAT6-/- cells. Since the promoters for Th2 cytokines such as IL-4, IL-5, IL-10, and IL-13 do not contain consensus BCL-6 DNA binding sites, we investigated whether BCL-6 might regulate the GATA-3 transcription factor that activates the expression of multiple Th2 cytokines. Consistent with the idea that BCL-6 represses GATA-3 expression, we found that GATA-3 levels are up-regulated in BCL-6-/-STAT6-/- CD4 T cells compared with STAT6-/- CD4 T cells. Retrovirus-mediated expression of BCL-6 in BCL-6-/-STAT6-/- T cells as well as developing wild-type Th2 cells leads to a potent repression of IL-4 and IL-10 secretion. Retrovirus-mediated expression of BCL-6 in both BCL-6-/ -STAT6-/- and wild-type T cells also leads to a significant decrease in GATA-3 protein levels. Surprisingly, BCL-6 does not appear to regulate GATA-3 mRNA levels and thus BCL-6 appears to regulate GATA-3 expression at a posttranscriptional level. Regulation of GATA-3 protein levels is likely a key mechanism for how BCL-6 regulates. Th2 cytokine expression and Th2 differentiation independently of STAT6. These data also point to a novel regulatory mechanism for BCL-6 separate from transcriptional repression.

Original languageEnglish
Pages (from-to)2435-2441
Number of pages7
JournalJournal of Immunology
Volume170
Issue number5
StatePublished - Mar 1 2003

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B-Cell Lymphoma
T-Lymphocytes
Interleukin-4
Cytokines
Th2 Cells
Retroviridae
Interleukin-10
GATA3 Transcription Factor
Interleukin-6
Regulatory B-Lymphocytes
GATA Transcription Factors
Repressor Proteins
Interleukin-13
Interleukin-5

ASJC Scopus subject areas

  • Immunology

Cite this

Kusam, S., Toney, L. M., Sato, H., & Dent, A. (2003). Inhibition of Th2 differentiation and GATA-3 expression by BCL-6. Journal of Immunology, 170(5), 2435-2441.

Inhibition of Th2 differentiation and GATA-3 expression by BCL-6. / Kusam, Saritha; Toney, Lisa M.; Sato, Hiroshi; Dent, Alexander.

In: Journal of Immunology, Vol. 170, No. 5, 01.03.2003, p. 2435-2441.

Research output: Contribution to journalArticle

Kusam, S, Toney, LM, Sato, H & Dent, A 2003, 'Inhibition of Th2 differentiation and GATA-3 expression by BCL-6', Journal of Immunology, vol. 170, no. 5, pp. 2435-2441.
Kusam, Saritha ; Toney, Lisa M. ; Sato, Hiroshi ; Dent, Alexander. / Inhibition of Th2 differentiation and GATA-3 expression by BCL-6. In: Journal of Immunology. 2003 ; Vol. 170, No. 5. pp. 2435-2441.
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