IL-19 and IL-20: two novel cytokines with importance in inflammatory diseases

Abstract

IL-19 and IL-20 are two cytokines that were discovered in 2000 and 2001, respectively. Based on the structure and location of their genes, their primary and secondary protein structures and the used receptor complexes, they were classified with IL-10, IL-22, IL-24, IL-26, IL-28 and IL-29 in the IL-10 family of cytokines, and form a subgroup with IL-24 within this family. IL-19 and IL-20 are produced by monocytes as well as non-immune tissue cells under inflammatory conditions. IL-19 and IL-20 act via a receptor complex that consists of the IL-20R1 and IL-20R2 chains. IL-20 is additionally able to signal via a second receptor complex (IL-22R1/IL-20R2). It is controversial whether or not IL-19 and IL-20 regulate the function of immune cells. However, the expression of their receptors aliments the perception that the cells of the skin, lungs and reproductive organs as well as various glands are major targets of these mediators. Results from animal experiments and massively increased expression of these mediators in human inflamed tissues support the assumption that they play an important role in the pathogenesis of a few inflammatory diseases. For this reason, the authors have reviewed the facts known at present regarding these cytokines and postulate that IL-19 and IL-20 are pharmacologically interesting distal elements of an inflammatory cascade.

Deficiency of IL-22 Contributes to a Chronic Inflammatory Disease: Pathogenetic Mechanisms in Acne Inversa

“…IL-22 and IL-20, although produced by different cell types (IL-22 as a T and NK cell cytokine, and IL-20 being produced by activated keratinocytes and dendritic cells) are two structurally and functionally related cytokines (28,29). The receptor complexes of both cytokines are known to be highly expressed in keratinocytes and are each composed of two different subunits: IL-22R1/IL-10R2 (receptor complex for IL-22), IL-20R1/IL-20R2 (receptor complex I for IL-20), and IL-22R1/IL-20R2 (receptor complex II for IL-20) (28,29).…”

“…The receptor complexes of both cytokines are known to be highly expressed in keratinocytes and are each composed of two different subunits: IL-22R1/IL-10R2 (receptor complex for IL-22), IL-20R1/IL-20R2 (receptor complex I for IL-20), and IL-22R1/IL-20R2 (receptor complex II for IL-20) (28,29). For IL-22, there is also a soluble, single-chain receptor called IL-22BP that acts as a high-affinity inhibitor of IL-22 activity (30)(31)(32)(33)(34).…”

Despite IFN-λ receptor expression, blood immune cells, but not keratinocytes or melanocytes, have an impaired response to type III interferons: implications for therapeutic applications of these cytokines

“…1,2 The aminoacid sequences of IFN-l2 and IFN-l3 are virtually identical (94%), those of IFN-l2 and IFN-l1 share 66%. These mediators are part of a larger family of structurally related cytokines called the class II cytokine family, which also contains the IL-10-related cytokines (IL-10, IL-19, IL-20, IL-22, IL-24 and IL-26), type I IFNs and IFN-g. [3][4][5] Within the class II cytokine family, IFN-ls form a theoretical bridge between IL-10-related cytokines on the one side and type I IFNs on the other, because they are closer to the first in terms of the structure of their encoding genes, their spatial protein structure and their receptor usage, but their activities mimic many functional aspects of type I IFNs. 1,2,[6][7][8] All three cytokines share the same receptor complex that consists of IFN-lR1 (also designated as IL-28R1) and IL-10R2, 1,2 with IL-10R2 also being part of the receptor complexes for IL-10, IL-22 and IL-26.…”

Distal and proximal interleukin (IL)-10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case–control study

“…Furthermore, the possibility of extending the haplotypic description to neighbouring genes, such as IL-19 should be considered, because skin tissues seem to represent a major target for IL-10-related cytokines, such as IL-19, IL-20, IL-22 and IL-24. [35][36][37] A multivariate analysis of the haplotypes was carried out in relation to skin type and number of nevi adjusted for multiple testing. The haplotypes are based on the gene variations IL-10À7400InDel, IL-10 À6752AT , IL-10 À3538AT , IL-10 À1087GA and IL-10 À597CA .…”