IL-23/IL-17 immunity as a hallmark of Crohn's disease

Background: We Studied the balance between ileal T-effector cells versus T-regulatory cells in active and inactive Crohn's disease (CD). Methods: we compared effector and regulatory T-cell-related markers such as interleukin (IL)-17, interferon (IFN)-gamma, IL-4, and Foxp3 transforming growth factor (TGF)-beta CTLA-4 and markers for innate immune activation such as IL-6, IL-10, IL-18, IL-23, tumor necrosis factor (TNF)-alpha, and IL-12p70 studied with immunohistochemistry and RT-PCR in ileal biopsies from patients with active or inactive CD and from control subjects. IL-17 in fecal samples was detected by ELISA. The effect of IL-17 oil IL-8 and TNF-alpha mRNA expression in epithelial cell line Caco-2 was studied. Results: The numbers of IL-4-, IL-17-. and IL-23(p19)-positive cells in the lamina propria were higher in patients with Cl), both active and inactive, than in the controls. mRNA expression of IL-17A IL-6, and Foxp3 was increased in the biopsies both from patients with active disease and those in remission, whereas mRNA expression of IL-23 was increased oil]), in active disease. Fecal IL-17 concentration was increase([ in patients with active disease. IL-17 enhanced the IL-8 and TNF-alpha response of the epithelial cell line to lipopolysaccharide (LPS) in vitro. Conclusions: Our findings suggest that activation of the IL-23/ IL-17 axis is fundamentally connected to the etiology of CD and may represent the basis for the relapsing nature of the disease by increasing the sensitivity of epithelium to microbial LPS.