Repression of interleukin-4 in T helper type 1 cells by Runx/Cbfβ binding to the Il4 silencer

Interferon γ (IFNγ) 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 Cbfβ- 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 Cbfβ 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

ナイザイセイ Foxp3+CD25+CD4+ セイギョセイ Tサイボウ ノ IL-2 ニ ヨル コウジョウセイ イジ ト IL-2 チュウワ ニ ヨル ジコ メンエキビョウ ノ ユウドウ ニ カンスル ケンキュウ

京都大学0048新制・課程博士博士(医学)甲第11437号医博第2860号新制||医||894(附属図書館)23080UT51-2005-D187京都大学大学院医学研究科病理系専攻(主査)教授 三森 経世, 教授 湊 長博, 教授 小柳 義夫学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA