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Publication : Foxo1 Promotes Th9 Cell Differentiation and Airway Allergy.

First Author  Buttrick TS Year  2018
Journal  Sci Rep Volume  8
Issue  1 Pages  818
PubMed ID  29339772 Mgi Jnum  J:270577
Mgi Id  MGI:6278779 Doi  10.1038/s41598-018-19315-z
Citation  Buttrick TS, et al. (2018) Foxo1 Promotes Th9 Cell Differentiation and Airway Allergy. Sci Rep 8(1):818
abstractText  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 IFNgamma 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.
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