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 on 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 CD, 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 only in active disease. Fecal IL-17 concentration was increased 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.
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 on 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 CD, 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 only in active disease. Fecal IL-17 concentration was increased 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.
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Authors: Jonas J W Kuiper; Jessica Van Setten; Stephan Ripke; Ruben Van 'T Slot; Flip Mulder; Tom Missotten; G Seerp Baarsma; Laurent C Francioli; Sara L Pulit; Carolien G F De Kovel; Ninette Ten Dam-Van Loon; Anneke I Den Hollander; Paulien Huis in het Veld; Carel B Hoyng; Miguel Cordero-Coma; Javier Martín; Victor Llorenç; Bharti Arya; Dhanes Thomas; Steven C Bakker; Roel A Ophoff; Aniki Rothova; Paul I W De Bakker; Tuna Mutis; Bobby P C Koeleman Journal: Hum Mol Genet Date: 2014-06-22 Impact factor: 6.150
Authors: Gilad Halpert; Tom Eitan; Elena Voronov; Ron N Apte; Lea Rath-Wolfson; Michael Albeck; Yona Kalechman; Benjamin Sredni Journal: J Biol Chem Date: 2014-04-24 Impact factor: 5.157