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

被引:166
作者
Holtta, Veera [1 ]
Klemetti, Paula [1 ,3 ]
Sipponen, Taina [2 ]
Kociubinski, Guillermo [1 ]
Westerholm-Ormio, Mia [3 ]
Solo, Horri [1 ]
Rasanen, Loura [1 ]
Kolho, Kaija-Leena [3 ]
Farkkila, Martti [2 ]
Savilahti, Erkki [3 ]
Vaarala, Outi [1 ]
机构
[1] Natl Publ Hlth Inst, Dept Virus Dis & Immunol, Immunol Lab, FIN-00300 Helsinki, Finland
[2] Univ Helsinki Hosp, Dept Med, Div Gastroenterol, Helsinki, Finland
[3] Univ Helsinki, Hosp Children & Adolescents, Helsinki, Finland
基金
芬兰科学院;
关键词
IL-17; Th17; cell; IL-23; Crohn's disease; inflammatory; bowel disease; Foxp3; immunohistochemistry;
D O I
10.1002/ibd.20475
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:1175 / 1184
页数:10
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