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J Allergy Clin Immunol. 2008 Jul;122(1):195-201, 201.e1-5. doi: 10.1016/j.jaci.2008.03.012. Epub 2008 Apr 18.

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

Author information

1
Division of Pulmonary and Critical Care Medicine, University of Rochester Medical Center, Rochester, NY, USA.

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.

PMID:
18423564
DOI:
10.1016/j.jaci.2008.03.012
[Indexed for MEDLINE]

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