NDLI: Foxo1 Is a T Cell-Intrinsic Inhibitor of the RORÎ³t-Th17 Program.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bismuth, Georges Lainé, Alexandra Lucas, Bruno Martin, Bruno Charvet, Céline Luka, Marine Auffray, Cédric Mir, Lucile
Description	Country affiliation: France Author Affiliation: Lainé A ( INSERM U1016, Institut Cochin, 75014 Paris, France); Martin B ( INSERM U1016, Institut Cochin, 75014 Paris, France); Luka M ( INSERM U1016, Institut Cochin, 75014 Paris, France); Mir L ( INSERM U1016, Institut Cochin, 75014 Paris, France); Auffray C ( INSERM U1016, Institut Cochin, 75014 Paris, France); Lucas B ( INSERM U1016, Institut Cochin, 75014 Paris, France); Bismuth G ( INSERM U1016, Institut Cochin, 75014 Paris, France); Charvet C ( INSERM U1016, Institut Cochin, 75014 Paris, France)
Abstract	An uncontrolled exaggerated Th17 response can drive the onset of autoimmune and inflammatory diseases. In this study, we show that, in T cells, Foxo1 is a negative regulator of the Th17 program. Using mixed bone marrow chimeras and Foxo1-deficient mice, we demonstrate that this control is effective in vivo, as well as in vitro during differentiation assays of naive T cells with specific inhibitor of Foxo1 or inhibitors of the PI3K/Akt pathway acting upstream of Foxo1. Consistently, expressing this transcription factor in T cells strongly decreases Th17 generation in vitro as well as transcription of both IL-17A and IL-23R RORÎ³t-target genes. Finally, at the molecular level, we demonstrate that Foxo1 forms a complex with RORÎ³t via its DNA binding domain to inhibit RORÎ³t activity. We conclude that Foxo1 is a direct antagonist of the RORÎ³t-Th17 program acting in a T cell-intrinsic manner.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	195
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Forkhead Transcription Factors Metabolism Nuclear Receptor Subfamily 1, Group F, Member 3 T-lymphocyte Subsets Th17 Cells Animals Cell Differentiation Genetics Cell Line Deficiency Immunophenotyping Interleukin-17 Lymphocyte Count Mice Mice, Knockout Antagonists & Inhibitors Chemistry Phenotype Phosphatidylinositol 3-kinases Promoter Regions, Genetic Protein Interaction Domains And Motifs Proto-oncogene Proteins C-akt Signal Transduction Cytology Immunology Transcription, Genetic Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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