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

• Published in: Gut Vol. 58; no. 9; pp. 1207 - 1217
• Main Authors: Dambacher, J, Beigel, F, Zitzmann, K, De Toni, E N, Göke, B, Diepolder, H M, Auernhammer, C J, Brand, S
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.09.2009; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Adolescent; Adult; Aged; Apoptosis - drug effects; Biological and medical sciences; Biotechnology; Blotting, Western; Cell Line; Cell Line, Tumor; Cell Proliferation - drug effects; Crohn Disease - immunology; Crohns disease; Cytokines; Epithelial Cells - chemistry; Epithelial Cells - immunology; Female; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunoglobulins; Immunohistochemistry; Inflammation; Inflammatory bowel disease; Interleukin-17 - immunology; Interleukins - genetics; Interleukins - immunology; Interleukins - pharmacology; Intestinal Mucosa - immunology; Kinases; Lymphocytes; Male; Medical sciences; Microscopy, Confocal; Middle Aged; Nuclear Receptor Subfamily 1, Group F, Member 3; Pathogenesis; Proteins; Receptors, Retinoic Acid - metabolism; Receptors, Thyroid Hormone - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - analysis; Signal transduction; Signal Transduction - physiology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Young Adult; Germany; Inflammation; Cytokine; Gastroenterology; Gut
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gut.2007.130112

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 RORγt, 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 RORγt-expressing Th17 cells in situ, supporting a role for this cell type in the pathogenesis of Crohn’s disease.