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.

Genome-wide screening in human growth plates during puberty in one patient suggests a role for RUNX2 in epiphyseal maturation.

In late puberty, estrogen decelerates bone growth by stimulating growth plate maturation. In this study, we analyzed the mechanism of estrogen action using two pubertal growth plate specimens of one girl at Tanner stage B2 and Tanner stage B3. Histological analysis showed that progression of puberty coincided with characteristic morphological changes: a decrease in total growth plate height (P=0.002), height of the individual zones (P<0.001), and an increase in intercolumnar space (P<0.001). Microarray analysis of the specimens identified 394 genes (72% upregulated and 28% downregulated) that changed with the progression of puberty. Overall changes in gene expression were small (average 1.38-fold upregulated and 1.36-fold downregulated genes). The 394 genes mapped to 13 significantly changing pathways (P<0.05) associated with growth plate maturation (e.g. extracellular matrix, cell cycle, and cell death). We next scanned the upstream promoter regions of the 394 genes for the presence of evolutionarily conserved binding sites for transcription factors implicated in growth plate maturation such as estrogen receptor (ER), androgen receptor, ELK1, STAT5B, cyclic AMP response element (CREB), and RUNX2. High-quality motif sites for RUNX2 (87 genes), ELK1 (43 genes), and STAT5B (31 genes), but not ER, were evolutionarily conserved, indicating their functional relevance across primates. Moreover, we show that some of these sites are direct target genes of these transcription factors as shown by ChIP assays.

The T-cell lymphokine interleukin-26 targets epithelial cells through the interleukin-20 receptor 1 and interleukin-10 receptor 2 chains.

The cellular members of the interleukin-10 (IL-10) cytokine family share sequence homology with IL-10, whereas their sites of expression and their functions are divergent. One of these factors, AK155 or IL-26, was discovered because of its overexpression in human T lymphocytes after growth transformation by the simian rhadinovirus herpesvirus saimiri. In addition, the gene is transcribed in various types of primary and immortalized T-cells. Here we describe epithelial cells, namely colon carcinoma cells and keratinocytes, as targets of this T-cellular lymphokine. Purified recombinant IL-26 induced the rapid phosphorylation of the signal transducer and activator of transcription factors 1 and 3. As a result, secretion of IL-10 and IL-8, as well as cell surface expression of CD54 were enhanced. Moreover, we show that the IL-26 protein binds to heparin, is released from the cell surface, and can be functionally inhibited by heparin. The sensitivity to recombinant IL-26 of various cell lines strictly correlated with the expression of the long chain of the IL-20 receptor. Because blocking antibodies against either the short chain of the IL-10 receptor or the long chain of the IL-20 receptor inhibited IL-26-dependent signal transduction, and transient expression of these receptor chains induced IL-26 responsivity in non-sensitive cells, we propose that the IL-20 receptor 1 and IL-10 receptor 2 chains participate in forming the IL-26 receptor. Targeting epithelial cells, the T-cell lymphokine IL-26 is likely to play a role in local mechanisms of mucosal and cutaneous immunity.

Interleukin-26.

Interleukin-26 (IL-26), initially termed AK155, is a cellular sequence homolog to IL-10 belonging to the IL-10 cytokine family. Together with the related genes for interferon-gamma and IL-22/IL-TIF, il-26 maps to the human chromosomal region 12q15. The il-26 gene is one of the few differentially expressed genes specifying human T cells after growth-transformation with herpesvirus saimiri, a tumor virus of neo-tropical squirrel monkeys. Only herpesvirus saimiri-transformed T cells have been found to strongly over-express il-26 and to release the protein into the tissue culture supernatant. In a series of other T-cell lines and in native peripheral blood cells, il-26 is transcribed at low levels, but it is not detectable in B cells. Similarly to IL-10, the IL-26 protein forms homo-dimers. IL-26 is a candidate to contribute to the transformed phenotype of human T cells after infection by herpesvirus saimiri. Moreover, the T-lymphokine IL-26 is highly likely to play a role in normal and pathological hematology or immunology.