The role of the novel Th17 cytokine IL-26 in intestinal inflammation

Background and aims: 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 ROR\textgreekgt, with an increased number
of colonic IL-26-expressing cells in active Crohn's
disease.Conclusion: 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 ROR\textgreekgt-expressing Th17 cells in situ,
supporting a role for this cell type in the pathogenesis of Crohn's
disease.