title: IL-15-dependent balance between Foxp3 and RORγt expression impacts inflammatory bowel disease.
abstract: The ability of CD4+ T cells to change their phenotype and to specialize into different functional subsets may enhance the risk of autoimmune diseases. Here we investigate how a pleiotropic cytokine interleukin (IL)-15 may modify the functional commitment of CD4+ T cells expressing the lineage-associated transcription factors: forkhead box P3 (Foxp3; Treg) and RORγt (Th17) in the context of inflammatory bowel disease (IBD). We demonstrate in mice that impaired delivery of IL-15 to CD4+ T cells in the colon downmodulates Foxp3 expression (diminishing STAT5 phosphorylation) and enhances RORγt expression (by upregulating the expression of Runx1). In consequence, CD4+ T cells deprived of IL-15 rapidly trigger IBD characterized by enhanced production of pro-inflammatory cytokines (interferon-γ, IL-6) and accumulation of Th1/Th17 cells. Overall, our findings indicate a potentially beneficial role of IL-15 in IBD by fine-tuning the balance between Treg and Th17 cells and controlling intestinal inflammation.
authors.affiliation: Unité de Biologie des Populations Lymphocytaires, Department of Immunology, Institut Pasteur, 25, rue du Docteur Roux, 75015 Paris, France.|CNRS, URA1961, 75015 Paris, France.
authors.forename: Milena J
authors.initials: MJ
authors.lastname: Tosiek
authors.affiliation: Unité d'Histopathologie Humaine et Modèles Animaux, Department of Infection and Epidemiology, Institut Pasteur, Hôpital Ste Anne, 75015 Paris, France.|Université Paris-Descartes, Hôpital Ste Anne, 75015 Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Fiette
authors.affiliation: Unité de Biologie des Populations Lymphocytaires, Department of Immunology, Institut Pasteur, 25, rue du Docteur Roux, 75015 Paris, France.|CNRS, URA1961, 75015 Paris, France.
authors.forename: Sary
authors.initials: S
authors.lastname: El Daker
authors.affiliation: CNRS, URA1961, 75015 Paris, France.|Unité de Développement des Tissus Lymphoïdes, Department of Immunology, Institut Pasteur, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Eberl
authors.affiliation: Unité de Biologie des Populations Lymphocytaires, Department of Immunology, Institut Pasteur, 25, rue du Docteur Roux, 75015 Paris, France.|CNRS, URA1961, 75015 Paris, France.
authors.forename: Antonio A
authors.initials: AA
authors.lastname: Freitas
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D003106:Colon / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000276:immunology*; D015536:Down-Regulation; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D019409:Interleukin-15; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3