IL-20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory disorders likes psoriasis, atherosclerosis, cancer, liver fibrosis, and RA.
IL-20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory disorders likes psoriasis, atherosclerosis, and renal failure.
Interleukin (IL)-10 family cytokines IL-10, IL-19, IL-20 and IL-24 have been implicated in autoimmune diseases and we have previously reported that genetic variants in the IL10 gene cluster were associated with psoriasis.
The IL-20 subfamily of cytokines has been reported to act at epithelial sites and contribute to psoriasis, wound healing, and anti-inflammatory effects during <i>S. aureus</i> infection.
Our results highlight the importance of gene assignment for translating GWAS findings into biologically meaningful mechanisms of disease and potential therapeutic targets; indeed, monoclonal antibody therapy targeting IL-20 is effective in the treatment of rheumatoid arthritis and psoriasis, both with strong GWAS associations to this region.
In our previous study, a single-nucleotide polymorphism (SNP) of IL-20-1723CG (rs1713239) was found to be associated with psoriasis progression, especially in those induced by upper respiratory tract infection.
Interleukin 19 (IL-19), IL-20 and IL-24 signal through type I and type II IL-20 receptors and are associated with inflammatory skin diseases such as psoriasis and atopic dermatitis.
The association between the IL-20-1723C→G allele on the 1q chromosome and psoriasis triggered or exacerbated by an upper respiratory tract infection in the Chinese Han population.
Here, we demonstrate that psoriasis mediators IL-17 and IL-22 synergistically induce the production of IL-20 subfamily proteins in cultured human keratinocytes.
This study suggests that different cytokines are players in the psoriasis pathogenesis although only the IL-10 family members IL-22 and IL-20 directly cause the characteristic epidermal alterations.
In the present study we tested the hypotheses that genetic variations of the IL-20-RI influence susceptibility to psoriasis and investigated single nucleotide polymorphisms (SNPs) in the IL20RA and IL20RB genes in psoriasis patients (n=254) and healthy controls (n=224).
Together, these data indicate that IL-20 may be an important effector cytokine in psoriasis, and that its inhibition may represent a potential therapeutic target.
Although association analysis of the IL-19 gene indicated that minor alleles of the IL-19 gene SNPs (rs2243188, rs2243169 and rs2243158) revealed protective effect to psoriasis and haplotype analysis of the IL-19 gene proved significant protective effect of the TGATA haplotype in case of late-onset disease, combined haplotype analysis of the IL-19 and -20 genes demonstrated that protective effect of the IL-19 gene is secondary to the susceptibility effect of the IL-20 gene.
Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis.