Foxo1 Promotes Th9 Cell Differentiation and Airway Allergy.

Autor:	Buttrick TS; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA., Wang W; Pulmonary and Critical Care, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA., Yung C; Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, NY, 10032, USA., Trieu KG; Pulmonary and Critical Care, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA., Patel K; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA., Khoury SJ; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.; Abu Haidar Neuroscience Institute, American University of Beirut Medical Center, Beirut, Lebanon., Ai X; Pulmonary and Critical Care, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA., Elyaman W; Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, NY, 10032, USA. we2152@cumc.columbia.edu.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2018 Jan 16; Vol. 8 (1), pp. 818. Date of Electronic Publication: 2018 Jan 16.
DOI:	10.1038/s41598-018-19315-z
Abstrakt:	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.
Databáze:	MEDLINE
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