IL-23–responsive innate lymphoid cells are increased in inflammatory bowel disease

TLDR

IL‑23/IL‑17 signaling drives inflammatory bowel disease, and recent work shows that IL‑23‑responsive innate lymphoid cells produce IL‑17, IL‑22, and IFN‑γ, yet their role in human disease is poorly understood. The study aimed to investigate the presence and function of IL‑23‑responsive ILCs in the intestines of healthy controls and IBD patients. Researchers examined intestinal samples from controls and IBD patients, profiling IL‑23‑responsive ILC populations and their cytokine gene expression. They found that IL‑23‑responsive ILCs are expanded in Crohn’s disease, with CD127⁺CD56⁻ cells producing IL‑17A/F and other pro‑inflammatory cytokines, indicating a potential contribution to intestinal inflammation and a novel therapeutic target.

Abstract

Results of experimental and genetic studies have highlighted the role of the IL-23/IL-17 axis in the pathogenesis of inflammatory bowel disease (IBD). IL-23-driven inflammation has been primarily linked to Th17 cells; however, we have recently identified a novel population of innate lymphoid cells (ILCs) in mice that produces IL-17, IL-22, and IFN-γ in response to IL-23 and mediates innate colitis. The relevance of ILC populations in human health and disease is currently poorly understood. In this study, we have analyzed the role of IL-23-responsive ILCs in the human intestine in control and IBD patients. Our results show increased expression of the Th17-associated cytokine genes IL17A and IL17F among intestinal CD3⁻ cells in IBD. IL17A and IL17F expression is restricted to CD56⁻ ILCs, whereas IL-23 induces IL22 and IL26 in the CD56⁺ ILC compartment. Furthermore, we observed a significant and selective increase in CD127⁺CD56⁻ ILCs in the inflamed intestine in Crohn's disease (CD) patients but not in ulcerative colitis patients. These results indicate that IL-23-responsive ILCs are present in the human intestine and that intestinal inflammation in CD is associated with the selective accumulation of a phenotypically distinct ILC population characterized by inflammatory cytokine expression. ILCs may contribute to intestinal inflammation through cytokine production, lymphocyte recruitment, and organization of the inflammatory tissue and may represent a novel tissue-specific target for subtypes of IBD.