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The role of the novel Th17 cytokine IL-26 in intestinal inflammation
  1. Julia Dambacher (julia.dambacher{at}med.uni-muenchen.de)
  1. Department of Medicine II, University-Hospital Munich-Grosshadern, University of Munich, Germany
    1. Florian Beigel
    1. Department of Medicine II, University-Hospital Munich-Grosshadern, University of Munich, Germany
      1. Kathrin Zitzmann
      1. Department of Medicine II, University-Hospital Munich-Grosshadern, University of Munich, Germany
        1. Enrico de Toni
        1. Department of Medicine II, University-Hospital Munich-Grosshadern, University of Munich, Germany
          1. Burkhard Göke
          1. Department of Medicine II, University-Hospital Munich-Grosshadern, University of Munich, Germany
            1. Helmut M. Diepolder
            1. Department of Medicine II, University-Hospital Munich-Grosshadern, University of Munich, Germany
              1. Christoph J. Auernhammer
              1. Department of Medicine II, University-Hospital Munich-Grosshadern, University of Munich, Germany
                1. Stephan Brand (stephan.brand{at}med.uni-muenchen.de)
                1. Department of Medicine II, University-Hospital Munich-Grosshadern, University of Munich, Germany

                  Abstract

                  Background/Aims: IL-26, a novel IL-10 like cytokine without murine homologue, is expressed in 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 RT-PCR, quantitative PCR, Western Blot and immunohistochemistry. Signal transduction was analysed by Western blot experiments and ELISA. Cell proliferation was measured by MTS 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 ERK-1/2 and SAPK/JNK MAP kinases, Akt, and STAT1/3. IL-26 stimulation increases the mRNA expression of proinflammatory cytokines but decreases cell proliferation. In inflamed colonic lesions of patients with Crohn's disease, we found an elevated IL-26 mRNA expression that correlated highly with the IL-8 and IL-22 expression. Immunohistochemical analysis demonstrated IL-26 protein expression in colonic T cells including RORgammat expressing Th17 cells 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 up-regulated 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, we demonstrate IL-26 expression in colonic RORgammat expressing Th17 cells in situ supporting a role for this cell type in the pathogenesis of Crohn's disease.

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