IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4(+) Th17 cells.
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.
Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, England, UK.
Margherita
M
Coccia
Oliver J
OJ
Harrison
Chris
C
Schiering
Mark J
MJ
Asquith
Burkhard
B
Becher
Fiona
F
Powrie
Kevin J
KJ
Maloy
D000818:Animals; D018956:CD5 Antigens / Q000378:metabolism*; D002470:Cell Survival; D003092:Colitis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D003106:Colon / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D006098:Granulocytes / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D044923:Helicobacter hepaticus / Q000472:pathogenicity; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D053573:Receptors, Interleukin-1 Type I / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*
D018956:CD5 Antigens; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I