The role of the novel Th17 cytokine IL-26 in intestinal inflammation.
OBJECTIVE
Interleukin 26 (IL-26), a novel IL-10-like cytokine without a murine homologue, is expressed in T helper 1 (Th1) and Th17 cells. Currently, its function in human disease is completely unknown. The aim of this study was to analyse its role in intestinal inflammation.


METHODS
Expression studies were performed by reverse transcription-PCR (RT-PCR), quantitative PCR, western blot and immunohistochemistry. Signal transduction was analysed by western blot experiments and ELISA. Cell proliferation was measured by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. IL-26 serum levels were determined by an immunoluminometric assay (ILMA).


RESULTS
All examined intestinal epithelial cell (IEC) lines express both IL-26 receptor subunits IL-20R1 and IL-10R2. IL-26 activates extracellular signal-related kinase (ERK)-1/2 and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) mitogen-activated protein (MAP) kinases, Akt and signal transducers and activators of transcription (STAT) 1/3. IL-26 stimulation increases the mRNA expression of proinflammatory cytokines but decreases cell proliferation. In inflamed colonic lesions of patients with Crohn's disease, an elevated IL-26 mRNA expression was found that correlated highly with the IL-8 and IL-22 expression. Immunohistochemical analysis demonstrated IL-26 protein expression in colonic T cells including Th17 cells expressing the orphan nuclear receptor RORgammat, with an increased number of colonic IL-26-expressing cells in active Crohn's disease.


CONCLUSIONS
Intestinal cells express the functional IL-26 receptor complex. IL-26 modulates IEC proliferation and proinflammatory gene expression and its expression is upregulated in active Crohn's disease, indicating a role for this cytokine system in the innate host cell response during intestinal inflammation. For the first time, IL-26 expression is demonstrated in colonic RORgammat-expressing Th17 cells in situ, supporting a role for this cell type in the pathogenesis of Crohn's disease.
Dambacher
J
J
University Hospital Munich-Grosshadern, Department of Medicine II, Ludwig-Maximilians-University, Munich, Germany.
Beigel
F
F
Zitzmann
K
K
De Toni
E N
EN
Göke
B
B
Diepolder
H M
HM
Auernhammer
C J
CJ
Brand
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003424:Crohn Disease / Q000276:immunology*; D004847:Epithelial Cells / Q000737:chemistry / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D020381:Interleukin-17 / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
C406767:IL26 protein, human; D020381:Interleukin-17; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; C539900:RORC protein, human; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone