Foxo1 促进 Th9 细胞分化和气道过敏。
Foxo1 Promotes Th9 Cell Differentiation and Airway Allergy.
机构信息
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Pulmonary and Critical Care, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
出版信息
Sci Rep. 2018 Jan 16;8(1):818. doi: 10.1038/s41598-018-19315-z.
T helper 9 (Th9) cells are effector CD4 T cells that are characterized by the production of interleukin-9 (IL-9) and have been associated with allergic responses. Here, we found that the expression of the transcription factor forkhead box O1 (Foxo1) was induced in Th9 and Foxo1 plays a crucial role in the differentiation of Th9 cells. Pharmacological inhibition of Foxo1 or genetic disruption of Foxo1 in CD4 T cells caused a reduction in IL-9 expression while upregulating IL-17A and IFNγ production. Furthermore, chromatin immunoprecipitation (ChIP) followed by luciferase assays revealed direct binding of Foxo1 to both the Il9 and Irf4 promoters and induces their transactivation. Lastly, adoptive transfer of Th9 cells into lungs induced asthma-like symptoms that were ameliorated by Foxo1 inhibitor, AS1842856. Together, our findings demonstrate a novel regulator of Th9 cells with a direct implication in allergic inflammation.
辅助性 T 细胞 9（Th9）细胞是效应 CD4 T 细胞，其特征在于白细胞介素 9（IL-9）的产生，并与过敏反应有关。在这里，我们发现转录因子叉头框 O1（Foxo1）的表达在 Th9 细胞中被诱导，Foxo1 在 Th9 细胞的分化中起着关键作用。Foxo1 的药理学抑制或在 CD4 T 细胞中的基因缺失导致 IL-9 表达减少，同时上调 IL-17A 和 IFNγ 的产生。此外，染色质免疫沉淀（ChIP）后进行荧光素酶测定显示 Foxo1 直接结合 Il9 和 Irf4 启动子，并诱导它们的反式激活。最后，将 Th9 细胞过继转移到肺部诱导哮喘样症状，Foxo1 抑制剂 AS1842856 可改善这些症状。总之，我们的研究结果表明 Foxo1 是 Th9 细胞的一种新型调节因子，直接参与过敏炎症。
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