IL-15-dependent balance between Foxp3 and RORγt expression impacts inflammatory bowel disease

Milena J. Tosiek (), Laurence Fiette, Sary El Daker, Gérard Eberl and Antonio A. Freitas ()
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Milena J. Tosiek: Unité de Biologie des Populations Lymphocytaires, Institut Pasteur
Laurence Fiette: Unité d’Histopathologie Humaine et Modèles Animaux, Institut Pasteur
Sary El Daker: Unité de Biologie des Populations Lymphocytaires, Institut Pasteur
Gérard Eberl: CNRS, URA1961
Antonio A. Freitas: Unité de Biologie des Populations Lymphocytaires, Institut Pasteur

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10888

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