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BATF3 is sufficient for the induction of Il9 expression and can compensate for BATF during Th9 cell differentiation.
Experimental & Molecular Medicine ( IF 12.8 ) Pub Date : 2019-11-27 , DOI: 10.1038/s12276-019-0348-6
Woo Ho Lee 1 , Sung Woong Jang 1 , Hyeong Su Kim 1 , So Hee Kim 1 , Jung In Heo 1 , Ga Eul Kim 1 , Gap Ryol Lee 1
Affiliation  

Th9 cells preferentially produce IL-9 and participate in allergic responses and asthma. Differentiation of Th9 cells is induced by IL-4 and TGF-β, and then the cells are amplified by OX40 signals. The transcription factors PU.1, IRF4, and BATF are required for Th9 differentiation. BATF3 is an AP-1 family transcription factor that is highly homologous to BATF; however, its role in Th9 cells is poorly defined. Here, we show that OX40 signaling induced the expression of Batf3 and that its overexpression in the presence or absence of OX40 signaling increased the expression of IL-9 in Th9 cells. BATF3 physically interacted with IRF4 and was bound to the Il9 locus. A transient reporter assay revealed that the BATF3–IRF4 complex induced Il9 promoter activity. BATF3 rescued Il9 expression and restored the capacity to induce the airway inflammation in Batf KO Th9 cells. Thus, BATF3 itself is sufficient for the induction of Th9 cell differentiation and can substitute for BATF during Th9 cell differentiation.



中文翻译:

BATF3 足以诱导 Il9 表达,并且可以在 Th9 细胞分化过程中补偿 BATF。

Th9 细胞优先产生 IL-9 并参与过敏反应和哮喘。Th9细胞的分化由IL-4和TGF-β诱导,然后细胞被OX40信号放大。Th9 分化需要转录因子 PU.1、IRF4 和 BATF。BATF3是与BATF高度同源的AP-1家族转录因子;然而,它在 Th9 细胞中的作用尚不明确。在这里,我们显示 OX40 信号传导诱导Batf3的表达,并且在存在或不存在 OX40 信号传导的情况下其过表达增加了 Th9 细胞中 IL-9 的表达。BATF3 与 IRF4 物理相互作用并与Il9基因座结合。瞬时报告分析显示 BATF3-IRF4 复合物诱导Il9启动子活性。BATF3 挽救了Il9表达并恢复了在Batf KO Th9 细胞中诱导气道炎症的能力。因此,BATF3本身足以诱导Th9细胞分化,并可在Th9细胞分化过程中替代BATF。

更新日期:2019-11-28
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