Interleukin-26, a Highly Cationic T-Cell Cytokine Targeting Epithelial Cells

Interleukin-26 (IL-26) is a member of the IL-10 cytokine family due to sequence homology. IL-26 was discovered, since the gene is strongly overexpressed in T cells which are growth transformed by herpesvirus saimiri. The IL-26 gene maps to human chromosome 12q15 between the genes for two other T-cellular class-II cytokines, namely interferon- γ(lFN-γ) and lL-22. IL-26, IL-22, and IFN-γ are co expressed by activated T cells and, especially, by Th17 cells. IL-26 forms homodimers and adheres to glycosaminoglycans on cell surfaces, presumably due to its positive charge. IL-26 specifically targets the lL-26-specific heterodimeric receptor complex consisting of IL-20R1 and IL-10R2 which is typically expressed on epithelial cells such as colon carcinoma cells or keratinocytes. IL-26 stimulation induces STAT1 and STAT3 phosphorylation, CD54 surface expression, and cytokine secretion as shown for IL-8 and IL-10. IL-26 seems to act as a cell surface-associated and rather proinflammatory T-cell cytokine at the epithelial barrier, possibly linking T-cell response with epithelial functions.