Yin-Yang 1 regulates effector cytokine gene expression and T(H)2 immune responses.

Abstract

BACKGROUND:

The transcription factor Yin-Yang 1 (YY-1) binds to the promoter regions of several T-cell cytokine genes, but the expression and contribution of this factor to cytokine gene expression and T-cell activation in vivo is not clear.

OBJECTIVE:

We sought to better define the role of YY-1 in T-cell gene regulation and allergic immune responses.

METHODS:

We studied cytokine gene expression in T lymphocytes isolated from wild-type mice and heterozygous littermates bearing 1 targeted yy-1 allele (yy-1(+/-) mice). T cells were stimulated with anti-T-cell receptor (anti-TCR) plus CD28 antibodies or with peptide antigen plus antigen-presenting cells by using newly generated yy-1(+/-) TCR transgenic mice. We also studied ovalbumin-driven allergic immune responses in a mouse model of asthma and YY-1 expression in lung tissue from human asthmatic subjects.

RESULTS:

CD4(+) T cells from yy-1(+/-) mice secreted significantly less IL-4 and IFN-gamma compared with wild-type littermates after TCR-dependent activation, whereas IL-2 production was not significantly affected. Both airway inflammation and recall splenocyte IL-4 production were inhibited in yy-1(+/-) mice, as was antigen-driven T-cell proliferation. YY-1 expression was higher in airway biopsy specimens from asthmatic compared with control subjects.

CONCLUSION:

These data indicate that YY-1 regulates T-cell cytokine gene expression and allergic immune responses in a gene dose-dependent manner.

• Authors: Jia Guo, Xin Lin, Marc A Williams, Qutayba Hamid, Steve N Georas
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 122 Issue 1 Pg. 195-201, 201.e1-5 (Jul 2008) ISSN: 1097-6825 [Electronic] United States
• PMID: 18423564 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• YY1 Transcription Factor
• Yy1 protein, mouse
• Interleukin-4
• Interferon-gamma
• Ovalbumin

Topics

• Animals
• Asthma (immunology, metabolism)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• Cell Proliferation
• Gene Expression
• Gene Expression Regulation (drug effects)
• Humans
• Interferon-gamma (genetics, immunology, metabolism)
• Interleukin-4 (genetics, immunology, metabolism)
• Lung (immunology, metabolism)
• Lymphocyte Activation
• Mice
• Mice, Transgenic
• Ovalbumin (immunology)
• Th2 Cells (immunology, metabolism)
• YY1 Transcription Factor (deficiency, genetics, metabolism)