Regulation of IL-10 gene expression in Th2 cells by Jun proteins

Zheng Yu Wang, Hiroshi Sato, Saritha Kusam, Sarita Sehra, Lisa M. Toney, Alexander Dent

Research output: Contribution to journalArticle

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Abstract

IL-10 is a key regulatory cytokine produced by T lymphocytes. Although Th2 cells are a major source of IL-10, little is known about IL-10 gene regulation in Th2 cells. High levels of IL-10 mRNA transcription are induced in the Th2 clone D10 after PMA plus ionomycin (P/I) stimulation; however we found that the IL-10 promoter was not inducible by P/I in D10 cells. We therefore sought regulatory regions in the IL-10 gene that could promote P/I-activated transcription in Th2 cells. Two strong DNase I-hypersensitive sites (DHSSs) were identified in the IL-10 gene in mouse T cells, and conserved noncoding sequences (CNSs) between the mouse and human IL-10 genes were also identified. One IL-10 DHSS maps within or next to a highly conserved CNS region, CNS-3. The CNS-3 region contains an AP-1 site that binds JunB and c-Jun proteins specifically in Th2 cells and not in Th1 cells. The CNS-3 element activates transcription from the IL-10 promoter after P/I stimulation and is responsive to c-Jun and JunB. Retroviral mediated-expression of either c-Jun or JunB in primary T cells led to a large increase in IL-10 expression, and inhibition of AP-1 activity by a dominant negative form of c-Jun in primary T cells strongly repressed IL-10 expression. IFN-γ was relatively unaffected by modulations in AP-1 activity. These data indicate that we have identified a novel regulatory element that can specifically activate transcription of the IL-10 gene in Th2 cells via the AP-1/Jun pathway.

Original languageEnglish
Pages (from-to)2098-2105
Number of pages8
JournalJournal of Immunology
Volume174
Issue number4
StatePublished - Feb 15 2005

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Th2 Cells
Interleukin-10
Gene Expression
Conserved Sequence
Proteins
Ionomycin
Transcription Factor AP-1
T-Lymphocytes
Genes
Deoxyribonuclease I
Proto-Oncogene Proteins c-jun
Th1 Cells
Nucleic Acid Regulatory Sequences

ASJC Scopus subject areas

  • Immunology

Cite this

Wang, Z. Y., Sato, H., Kusam, S., Sehra, S., Toney, L. M., & Dent, A. (2005). Regulation of IL-10 gene expression in Th2 cells by Jun proteins. Journal of Immunology, 174(4), 2098-2105.

Regulation of IL-10 gene expression in Th2 cells by Jun proteins. / Wang, Zheng Yu; Sato, Hiroshi; Kusam, Saritha; Sehra, Sarita; Toney, Lisa M.; Dent, Alexander.

In: Journal of Immunology, Vol. 174, No. 4, 15.02.2005, p. 2098-2105.

Research output: Contribution to journalArticle

Wang, ZY, Sato, H, Kusam, S, Sehra, S, Toney, LM & Dent, A 2005, 'Regulation of IL-10 gene expression in Th2 cells by Jun proteins', Journal of Immunology, vol. 174, no. 4, pp. 2098-2105.
Wang ZY, Sato H, Kusam S, Sehra S, Toney LM, Dent A. Regulation of IL-10 gene expression in Th2 cells by Jun proteins. Journal of Immunology. 2005 Feb 15;174(4):2098-2105.
Wang, Zheng Yu ; Sato, Hiroshi ; Kusam, Saritha ; Sehra, Sarita ; Toney, Lisa M. ; Dent, Alexander. / Regulation of IL-10 gene expression in Th2 cells by Jun proteins. In: Journal of Immunology. 2005 ; Vol. 174, No. 4. pp. 2098-2105.
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