| First Author | Tosiek MJ | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10888 | PubMed ID | 26964669 |
| Mgi Jnum | J:236563 | Mgi Id | MGI:5806382 |
| Doi | 10.1038/ncomms10888 | Citation | Tosiek MJ, et al. (2016) IL-15-dependent balance between Foxp3 and RORgammat expression impacts inflammatory bowel disease. Nat Commun 7:10888 |
| abstractText | 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 RORgammat (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 RORgammat 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-gamma, 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. |
