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


CONCLUSIONS
These data indicate that YY-1 regulates T-cell cytokine gene expression and allergic immune responses in a gene dose-dependent manner.
Guo
Jia
J
Division of Pulmonary and Critical Care Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Lin
Xin
X
Williams
Marc A
MA
Hamid
Qutayba
Q
Georas
Steve N
SN
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D050986:YY1 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin