Interleukin-26

Interleukins (from Latin/Greek inter = between; leukos = white; kinein = to move) are a group of endogenous, short-chain regulatory proteins (cytokines) of the immune system (IL1-IL38). Interleukins are mediators for induction, course and control of T-cell-mediated cytotoxic immune reactions as well as B-cell activation (antibody production). They are mainly formed and secreted by stimulated leukocytes, monocytes and macrophages. So far, about 38 different interleukins have been clearly identified. Each cytokine of the interleukin group is nomenclatically assigned a number for its classification (IL-1 to IL-38).

Some structurally related substances have been grouped into families. Their members often have a similar function or participate in the fine regulation of immune reactions, for example by regulating the synthesis of related interleukins. Interleukin-26 (IL-26) is a cationic cytokine that is a member of the IL-10 cytokine family due to its structure and homology to IL-10.

The interleukin-26 gene is located on chromosome 12q15, between the genes for 2 other class II cytokines, namely interferon-gamma (lFN-γ) and interleukin-22.

IL-26 is predominantly expressed by T cells, by various subtypes of natural killer cells, by monocytes, and by fibroblast and synoviocytes. Activated Th17 cells coexpress besides IL-26, IL-22, and IFN-gamma.

The heterodimeric RIL-26 receptor consists of the ligand-binding receptor chain IL-20R1 and the accessory chain IL-10R2. The receptor is expressed mainly by epithelial cells, such as colon cancer cells, keratinocytes and fibroblasts, which are stimulated to form and secrete IL-1beta, IL-8 and TNF-alpha.

IL-26 increases the chemotaxis of human neutrophil granulocytes. Studies in inflammatory diseases are rather rare so far. Some studies show the involvement of IL-26 in rheumatoid arthritis, inflammatory bowel disease and "non-allergic" childhood intrinsic asthma.

In cell culture, IL-26 has been shown to have both replication-promoting and replication-inhibiting effects on various viruses. These results indicate the importance of IL-26 for the development of viral infections in their early stages. The antiviral effect seems to be specific for certain virus types. For example, it has been shown to be specific for human cytomegalovirus (hCMV), but not for herpes simplex virus type 1.

It could be shown that IL-26 leads to the induction of antiviral cytokines in virus-infected - but not in non-virus-infected cells. IL-26 thus appears to be essential for the early phase of certain virus infections. IL-26 enhances the expression of IFN-beta1 and IFN-responsive genes, thus additionally supporting antiviral cellular functions.

1. Braum O et al (2012) Interleukin-26, a highly cationic T-cell cytokine targeting epithelial cells. Antiinflammatory Antiallergy Agents Med Chem 11:221-229.
2. Braum O et al (2013) The cationic cytokine IL-26 differentially modulates virus infection in culture. PLoS One 8:e70281.
3. Che KF et al (2014) Interleukin-26 in antibacterial host defense of human lungs. Effects on neutrophil mobilization. At J Respir Crit Care Med 190:1022-1031.
4. Donnelly RP et al (2010) Interleukin-26: an IL-10-related cytokine produced by Th17 cells. Cytokine growth factor Rev 21:393-401.
5. Fickenscher H et al (2004) Interleukin-26 Int Immunopharmacol 4:609-613.
6. Hör S et al (2004) The T-cell lymphokine interleukin-26 targets epithelial cells through the interleukin-20 receptor 1 and interleukin-10 receptor 2 chains. J Biol Chem 279):33343-33351.
7. Konradsen JR et al (2016) The cytokine interleukin-26 as a biomarker in pediatric asthma. Respir Res 17:32.
8. Meller S et al (2015) T(H)17 cells promote microbial kiling and innate immune sensing of DNA via interleukin 26 Nat Immunol 16:970-979 .
9. Tengvall S et al. (2016) Interleukin-26: An Emerging Player in Host Defense and Inflammation. J Innate Immun 8:15-22.