Cytokine genes are regulated by multiple regulatory elements that confer tissue-specific and activation-dependent expression. The cis-regulatory elements of the gene encoding IL-9, a cytokine that promotes allergy, autoimmune inflammation and tumor immunity, have not been defined. Here we identify an enhancer (CNS-25) upstream of the Il9 gene that binds most transcription factors (TFs) that promote Il9 gene expression. Deletion of the enhancer in the mouse germline alters transcription factor binding to the remaining Il9 regulatory elements, and results in diminished IL-9 production in multiple cell types including Th9 cells, and attenuates IL-9-dependent immune responses. Moreover, deletion of the homologous enhancer (CNS-18) in primary human Th9 cultures results in significant decrease of IL-9 production. Thus, Il9 CNS-25/IL9 CNS-18 is a critical and conserved regulatory element for IL-9 production.

中文翻译：

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保守的增强子调节多个谱系中的Il9表达。

细胞因子基因受多种调控元件的调控，这些调控元件赋予组织特异性和活化依赖性表达。尚未定义编码IL-9（一种促进过敏，自身免疫炎症和肿瘤免疫的细胞因子）的基因的顺式调控元件。在这里，我们确定了一个增强子（CNS-25）在Il9基因的上游，与大多数促进Il9基因表达的转录因子（TFs）结合。小鼠种系中增强子的缺失改变了转录因子与其余Il9调控元件的结合，导致包括Th9细胞在内的多种细胞类型中IL-9的产生减少，并减弱了IL-9依赖性免疫应答。而且，在原代人Th9培养物中同源增强子（CNS-18）的缺失导致IL-9产生的显着降低。因此，