Cutting Edge: Immune Cells as Sources and Targets of the IL-10 Family Members?

Abstract

This study investigated the expression of five novel human IL-10-related molecules and their receptors in blood mononuclear cells. IL-19 and IL-20 were found to be preferentially expressed in monocytes. IL-22 and IL-26 (AK155) expression was exclusively detected in T cells, especially upon type 1 polarization, and in NK cells. IL-24 (melanoma differentiation-associated gene 7) expression was restricted to monocytes and T cells. Detection of these molecules in lymphocytes was predominantly linked to cellular activation. Regarding T cells, IL-26 was primarily produced by memory cells, and its expression was independent on costimulation. In contrast to the high expression of receptors for IL-10 homologs in different tissues and cell lines, monocytes and NK, B, and T cells showed clear expression only of IL-10R1, IL-10R2, and IL-20R2. In these cells, IL-20R2 might be part of a still-unknown receptor complex. Therefore, immune cells may represent a major source but a minor target of the novel IL-10 family members.

Combined haplotype analysis of the interleukin-19 and -20 genes: relationship to plaque-type psoriasis

“…6,7 has been found to be preferentially expressed in monocytes and its main targets are keratinocytes, where IL-20 binds type I IL-20R (IL-20Ra and -20Rb) and type II IL-20R (IL-20Rb and -22R) complexes. 6,8,9 Binding of the IL-20 in human HaCaT keratinocytic cell line results in STAT 3 phosphorylation and activation of a promoter including STAT-binding sites. 6 Microarray and RT-PCR analyses in HaCaT cells have demonstrated that the expression of several genes involved in inflammation are increased in response to IL-20 and therefore this cytokine may modulate the inflammatory response in the skin.…”

“…IL-19 has been detected in immune cells, such as LPS-or GM-CSF-activated and resting monocytes, and at lower level in resting and stimulated B cells. 7,8 This cytokine binds to the type I IL-20R complex and modulates gene expression in responsive cell types through activation of the STAT 1 and STAT 3 signal transduction pathway. [9][10][11] Sharing the same receptor complex with IL-20 suggests that IL-19 may have partially overlapping biological activities with IL-20.…”

Association analysis of IL20RA and IL20RB genes in psoriasis

“…[4][5][6] The expression levels of IL-19, IL-20 and IL-24 in lesional skin of psoriasis patients are increased compared to healthy skin. 2,[7][8][9][10][11] Two independent studies have demonstrated that overexpression of IL-20 in transgenic mice induces a skin phenotype similar to psoriasis. 2,5 Both in vitro and in vivo, IL-20 promotes hyperproliferation and abnormal differentiation of keratinocytes that are characteristic features of psoriasis.…”

Conservation of the genomic structure and receptor-mediated signaling between human and rat IL-24

“…10 Once bound, IL-24 signals through the heterodimeric receptors, leading to the phosphorylation and activation of the JAK/ STAT pathway. 10,12 In contrast to the IL-10 receptor (IL-10R1/IL-10R2), which is constitutively expressed by most hemopoietic cells, 14 constitutive expression of the IL-24 receptors (IL-20R2 with at least one of the R1 chains) was not found in the immune cells tested, 11 but was detected in various nonhemopoietic tissues including lung, testis, ovary and skin, indicating a pleotropic role of IL-24 outside of the immune system. 15 Human IL-24 gene originally was known as mda-7 (melanoma differentiation associated gene-7), which was identified by subtraction hybridization as a gene whose expression was upregulated in H0-1 melanoma cells when the cells were induced to terminal differentiation by the combination of IFN-b and mezerein.…”

“…7 Expression of IL-24 was detected in spleen, thymus, 8 melanocytes, 9 ConA activated human PBMC cells, 10 LPS-treated monocytes and anti-CD3-treated T cells. 11 Two heterodimeric receptors for IL-24 have been identified, IL-20R1/IL-20R2 and IL-22R/IL-20R2, 10,12 the subunits of which belong to the class II cytokine receptor family. 13 IL-24 can bind to the IL-20R2 subunit alone, but co-expression of either IL-20R1 or IL-22R not only increases the binding affinity but also is necessary for receptor activation.…”