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 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.
Hölttä
Veera
V
Laboratory for Immunobiology, Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland.
Klemetti
Paula
P
Sipponen
Taina
T
Westerholm-Ormio
Mia
M
Kociubinski
Guillermo
G
Salo
Harri
H
Räsänen
Laura
L
Kolho
Kaija-Leena
KL
Färkkilä
Martti
M
Savilahti
Erkki
E
Vaarala
Outi
O
D000328:Adult; D000368:Aged; D018938:Caco-2 Cells; D003424:Crohn Disease / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D006801:Humans; D007082:Ileum / Q000276:immunology; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D053759:Interleukin-23; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma