Published online
doi:10.1084/jem.20062456
The Journal of Experimental Medicine, Vol. 204, No. 8, 1749-1755
The Rockefeller University Press, 0022-1007 $30.00
© Naoe et al.
Repression of interleukin-4 in T helper type 1 cells by Runx/Cbfß binding to the Il4 silencer
Yoshinori Naoe1,
Ruka Setoguchi1,
Kaori Akiyama1,2,
Sawako Muroi2,
Masahiko Kuroda3,
Farah Hatam4,
Dan R. Littman4, and
Ichiro Taniuchi1,2
1 Institute of Physical and Chemical Research, Research Center for Allergy and Immunology, Turumi-ku, Yokohama, Kanagawa 230-0045, Japan
2 Precursory Research for Embryonic Sciences and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan
3 Tokyo Medical University, Shinjuku-ku, Tokyo 160-8402, Japan
4 Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016
CORRESPONDENCE Ichiro Taniuchi:taniuchi{at}rcai.riken.jp
Interferon
(IFN
) is the hallmark cytokine produced by T helper type 1 (Th1) cells, whereas interleukin (IL)-4 is the hallmark cytokine produced by Th2 cells. Although previous studies have revealed the roles of cytokine signaling and of transcription factors during differentiation of Th1 or Th2 cells, it is unclear how the exclusive expression pattern of each hallmark cytokine is established. The DNaseI hypersensitivity site IV within the mouse Il4 locus plays an important role in the repression of Il4 expression in Th1 cells, and it has been named the Il4 silencer. Using Cbfß- or Runx3-deficient T cells, we show that loss of Runx complex function results in derepression of IL-4 in Th1 cells. Binding of Runx complexes to the Il4 silencer was detected in naive CD4+ T cells and Th1 cells, but not in Th2 cells. Furthermore, enforced expression of GATA-3 in Th1 cells inhibited binding of Runx complexes to the Il4 silencer. Interestingly, T cell–specific inactivation of the Cbfß gene in mice led to elevated serum immunoglobulin E and airway infiltration. These results demonstrate critical roles of Runx complexes in regulating immune responses, at least in part, through the repression of the Il4 gene.
Abbreviations used: ChIP, chromatin immunoprecipitation; CNS, conserved noncoding sequence; HS, hypersensitive.

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