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Foxo1 Promotes Th9 Cell Differentiation and Airway Allergy.

ABSTRACT: 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 IFN? 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.

SUBMITTER: Buttrick TS

PROVIDER: S-EPMC5770389 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Foxo1 Promotes Th9 Cell Differentiation and Airway Allergy.

Buttrick Thomas S TS Wang Wei W Yung Christina C Trieu Kenneth G KG Patel Kruti K Khoury Samia J SJ Ai Xingbin X Elyaman Wassim W

Scientific reports 20180116 1

T helper 9 (Th9) cells are effector CD4<sup>+</sup> 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<sup>+</sup> T cells caused a reduction in IL-9 expression while upregulating ...[more]

PMID: 29339772

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