WNT2B High‑expressed Fibroblasts Induce the Fibrosis of IBD by Promoting NK Cells Secreting IL-33

Fibrosis is an important pathological change in inflammatory bowel disease (IBD), but the mechanism has yet to be elucidated. WNT2B high‑expressed fibroblasts are enriched in IBD intestinal tissues, although the precise function of this group of fibroblasts remains unclear. This study investigated whether WNT2B high‑expressed fibroblasts aggravated intestinal tissue damage and fibrosis. Our study provides evidence that WNT2B high‑expressed fibroblasts and NK cells were enriched in colitis tissue of patients with IBD. WNT2B high‑expressed fibroblasts secreted wnt2b, which bound to FZD4 on NK cells and activated the NF-κB and STAT3 pathways to enhance IL-33 expression. TCF4, a downstream component of the WNT/β-catenin pathway, bound to p65 and promoted binding to IL-33 promoter. Furthermore, Salinomycin, an inhibitor of the WNT/β-catenin pathway, inhibited IL-33 secretion in colitis, thereby reducing intestinal inflammation.Knocking down WNT2B reduces NK cell infiltration and IL-33 secretion in colitis, and reduce intestinal inflammation and fibrosis. In conclusion, WNT2B high‑expressed fibroblasts activate NK cells by secreting wnt2b, which activates the WNT/β-catenin and NF-κB pathways to promote IL-33 expression and secretion, potentially culminating in the induction of colonic fibrosis in IBD.