Interleukin 20

Interleukin 20 (IL-20) is a novel member of the expanding family of IL-10-like cytokines, which includes IL-19, IL-22/IL-TIF, MDA-7/R-10, and AK155.^1-6 The IL-20 receptor (IL-20 R) is a heterodimer of two orphan class II cytokine receptors, designated IL-20 R alpha and IL-20 R beta.¹ Both receptor subunits are required for IL-20 binding.^7,8

Both the human and the mouse IL-20 pre-proteins are comprised of 176 amino acids (aa) with predicted signal peptides of aa 1-24 and mature proteins comprising aa 25-176. IL-20, like IL-19, contains six conserved cysteine residues, which are predicted to form three intramolecular disulfide bonds (see Figure 1). In contrast, IL-10 has only four conserved cysteine residues. It is presumed that the bioactive form of IL-20 is a non-covalently linked homodimer, similar to IL-10. Human and mouse IL-20 lack a potential N-linked glycosylation site. Mature human and mouse IL-20 display 74% aa identity and are most homologous to IL-19, sharing about 40% aa identity. IL-20 is also related to IL-22/IL-TIF, MDA-7/R-10, AK155, and IL-10, displaying 25-33% homology.

Although the physiological function of IL-20 has not been identified, three lines of evidence support a role for IL-20 and its receptor in inflammatory skin diseases such as psoriasis. For example, overexpression of IL-20 in transgenic mice results in neonatal lethality with skin abnormalities similar to those observed in human psoriatic skin. These include several hallmark characteristics of this multigenic disease such as increased proliferation of keratinocytes in the basal and suprabasal layers of the epidermis, aberrant epidermal differentiation, and infiltration of immune cells into the skin. Additionally, the expression of both IL-20 receptor subunits is markedly up-regulated in human psoriatic skin compared to normal skin. Finally, recombinant IL-20 enhances the expression of several proinflammatory genes, such as TNF-alpha, MRP-14/S100A9, and MCP-1 in HaCaT keratinocyte cells stimulated with IL-1 alpha.

Figure 1. Multiple Alignment Mapping of the IL-10 Protein Family Sequence of human IL-20 and its alignment with two other human members of the IL-10 protein family. Asterisks denote conserved residues. Colons represent highly conserved residues, Dots represent conservative substitutions. The arrow indicates the experimentally determined signal sequence cleavage site of IL-20. Underlines show the helical regions of IL-10. The location of conserved cysteines is indicated in bold blue type. [Figure is adapted from Blumberg, H. et al. (2001) Cell 104:9.]

References

1. Blumberg, H. et al. (2001) Cell 104:9.
2. Jiang, H. et al. (1995) Oncogene 11:2477.
3. Knappe, A. et al. (2000) J. Virol. 74:3881.
4. Gallagher, G. et al. (2000) Genes Immunity 1:442.
5. Dumoutier, L. et al. (2000) Proc. Natl. Acad. Sci. USA 97:10144.
6. Xie, M. et al. (2000) J. Biol. Chem. 275:31335.
7. U.S Patent No. 5,945,511 (1999).
8. International Patent Application WO/99/46379 (1999).