Deletion of a conserved Il4 silencer impairs T helper type 1-mediated immunity
Deletion of a conserved Il4 silencer impairs T helper type 1-mediated immunity
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DOI：
10.1038/ni1135
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发表时间：
2004-12-01
影响因子：
30.5
通讯作者：
Rao, A
中科院分区：
文献类型：
--
作者：
Ansel, KM;Greenwald, RJ;Rao, A
辅助T细胞分化涉及基因表达的沉默以及激活。我们已经确定了一个保守的沉默的基因编码白细胞介素4（IL 4）标记的DNA酶I超敏反应（HS IV）和允许的染色质结构中的所有辅助T细胞。HS IV的缺失增加了幼稚T细胞的Il 4和Il 13转录，并导致体外辅助性T细胞2型倾斜。HS IV在1型辅助性T细胞分化过程中控制IL 4沉默，因为表达干扰素-γ的HS IV缺陷型1型辅助性T细胞在体外和体内也产生丰富的白细胞介素4。尽管安装了一个有力的干扰素-γ反应，HS IV缺陷型小鼠更容易感染利什曼原虫比野生型同窝对照小鼠，显示IL 4沉默的T辅助细胞1型介导的免疫的关键功能。
Helper T cell differentiation involves silencing as well as activation of gene expression. We have identified a conserved silencer of the gene encoding interleukin 4 (Il4) marked by DNase I hypersensitivity (HS IV) and permissive chromatin structure in all helper T cells. Deletion of HS IV increased Il4 and Il13 transcription by naive T cells and led to T helper type 2 skewing in vitro. HS IV controlled Il4 silencing during T helper type 1 differentiation, as HS IV-deficient T helper type 1 cells that expressed interferon-gamma also produced abundant interleukin 4 in vitro and in vivo. Despite mounting a vigorous interferon-gamma response, HS IV-deficient mice were more susceptible to Leishmania major infection than were wild-type littermate control mice, showing a critical function for Il4 silencing in T helper type 1-mediated immunity.