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A role for BATF3 in TH9 differentiation and T-cell-driven mucosal pathologies.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2019-Jan-07 , DOI: 10.1038/s41385-018-0122-4
Masato Tsuda 1, 2 , Hussein Hamade 1 , Lisa S Thomas 1 , Brenda C Salumbides 1 , Alka A Potdar 1 , Michelle H Wong 1 , Jordan S Nunnelee 1 , Jasmine T Stamps 1 , Anita Vibsig Neutzsky-Wulff 1 , Robert J Barrett 1, 3 , Yizhou Wang 4 , Jie Tang 4 , Vincent A Funari 4 , Stephan R Targan 1 , Kathrin S Michelsen 1
Affiliation  

T helper 9 (TH9) cells are important for the development of inflammatory and allergic diseases. The TH9 transcriptional network converges signals from cytokines and antigen presentation but is incompletely understood. Here, we identified TL1A, a member of the TNF superfamily, as a strong inducer of mouse and human TH9 differentiation. Mechanistically, TL1A induced the expression of the transcription factors BATF and BATF3 and facilitated their binding to the Il9 promoter leading to enhanced secretion of IL-9. BATF- and BATF3-deficiencies impaired IL-9 secretion under TH9 and TH9-TL1A-polarizing conditions. In vivo, using a T-cell transfer model, we demonstrated that TL1A promoted IL-9-dependent, TH9 cell-induced intestinal and lung inflammation. Neutralizing IL-9 antibodies attenuated TL1A-driven mucosal inflammation. Batf3-/- TH9-TL1A cells induced reduced inflammation and cytokine expression in vivo compared to WT cells. Our results demonstrate that TL1A promotes TH9 cell differentiation and function and define a role for BATF3 in T-cell-driven mucosal inflammation.

中文翻译:

BATF3 在 TH9 分化和 T 细胞驱动的粘膜病理学中的作用。

T 辅助细胞 9 (T H 9) 细胞对于炎症和过敏性疾病的发展很重要。T H 9 转录网络会聚来自细胞因子和抗原呈递的信号,但尚未完全了解。在这里,我们将 TNF 超家族的成员 TL1A 鉴定为小鼠和人类 T H 9 分化的强诱导剂。从机制上讲,TL1A 诱导转录因子 BATF 和 BATF3 的表达,并促进它们与 Il9 启动子的结合,从而增强 IL-9 的分泌。在 T H 9 和 T H 9-TL1A 极化条件下,BATF 和 BATF3 缺陷会损害 IL-9 的分泌。在体内,使用 T 细胞转移模型,我们证明 TL1A 促进 IL-9 依赖性,TH 9 细胞诱导的肠道和肺部炎症。中和 IL-9 抗体可减轻 TL1A 驱动的粘膜炎症。与 WT 细胞相比, Batf3 -/- T H 9-TL1A 细胞在体内诱导炎症和细胞因子表达减少。我们的结果表明 TL1A 促进 T H 9 细胞分化和功能,并确定 BATF3 在 T 细胞驱动的粘膜炎症中的作用。
更新日期:2019-01-26
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