IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4(+) Th17 cells

• Published in: The Journal of experimental medicine Vol. 209; no. 9; pp. 1595 - 1609
• Main Authors: Coccia, Margherita, Harrison, Oliver J, Schiering, Chris, Asquith, Mark J, Becher, Burkhard, Powrie, Fiona, Maloy, Kevin J
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 27-08-2012
• Subjects: Animals; CD5 Antigens - metabolism; Cell Survival; Colitis - immunology; Colitis - metabolism; Colitis - microbiology; Colon - immunology; Colon - microbiology; Colon - pathology; Granulocytes - immunology; Helicobacter hepaticus - pathogenicity; Helicobacter Infections - immunology; Helicobacter Infections - metabolism; Helicobacter Infections - pathology; Immunity, Innate; Interleukin-17 - metabolism; Interleukin-1beta - metabolism; Interleukin-23 - metabolism; Lymphocytes - immunology; Mice; Mice, Inbred C57BL; Receptors, Interleukin-1 - metabolism; Receptors, Interleukin-1 Type I - metabolism; Th17 Cells - immunology; Th17 Cells - metabolism
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20111453

Although very high levels of interleukin (IL)-1β are present in the intestines of patients suffering from inflammatory bowel diseases (IBD), little is known about the contribution of IL-1β to intestinal pathology. Here, we used two complementary models of chronic intestinal inflammation to address the role of IL-1β in driving innate and adaptive pathology in the intestine. We show that IL-1β promotes innate immune pathology in Helicobacter hepaticus-triggered intestinal inflammation by augmenting the recruitment of granulocytes and the accumulation and activation of innate lymphoid cells (ILCs). Using a T cell transfer colitis model, we demonstrate a key role for T cell-specific IL-1 receptor (IL-1R) signals in the accumulation and survival of pathogenic CD4(+) T cells in the colon. Furthermore, we show that IL-1β promotes Th17 responses from CD4(+) T cells and ILCs in the intestine, and we describe synergistic interactions between IL-1β and IL-23 signals that sustain innate and adaptive inflammatory responses in the gut. These data identify multiple mechanisms through which IL-1β promotes intestinal pathology and suggest that targeting IL-1β may represent a useful therapeutic approach in IBD.