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

TLDR

High intestinal IL‑1β levels are observed in inflammatory bowel disease, yet its specific contribution to intestinal pathology remains unclear. The study aims to determine how IL‑1β drives innate and adaptive intestinal pathology using two chronic inflammation models. The authors employed two complementary chronic intestinal inflammation models to investigate IL‑1β’s role in intestinal disease. IL‑1β drives chronic intestinal inflammation by recruiting granulocytes, activating innate lymphoid cells, promoting Th17 responses from CD4⁺ T cells, and synergizing with IL‑23, thereby sustaining innate and adaptive pathology and suggesting IL‑1β blockade as a potential IBD therapy.

Abstract

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.