Human Interleukin-19: Structure, Function and Disease Associations

Grant      Gallagher; Joyce      Eskdale; William      Jordan; Michele      Boniotto; Michelle      Rodia; Danielle      Kellner; Ellen      Witte; Robert      Sabat; Kerstin      Wolk

Abstract

Interleukin(IL) -19 is a member of the recently described IL-10 family of cytokines. Based on the genomic localization of its gene, its structure, conserved amino acids, cellular sources and receptor, IL-19 forms a subfamily with IL- 20 and IL-24. The IL-19-encoding gene comprises seven exons and is located on chromosome 1. Secreted IL-19 is composed of 159 amino acids that form an α-helical structure. IL-19 is produced by activated monocytes, and to a lesser extent, by B cells. As known so far, IL-19 functions through a receptor complex composed of IL-20R1 and IL-20R2, which is also utilized by IL-20 and IL-24. High levels of both receptor chains are present in several stromal tissues including the skin, lungs, and tissues from the reproductive organs. However, no expression is found in any immune cell population. Nonetheless, all effects of IL-19 described so far concern immune cells. Such conflicting data may be due to the existence of an additional (so far undiscovered) receptor complex for IL-19, or to the ability of the known IL-19 receptor to mediate its effects when present on the cell surface at a very low density. IL-19 has been shown to enhance the production of Th2 cytokines in T cells. Furthermore, it induced IL-10 expression in monocytes. Apart from the implied role for IL-19 in atopic and allergic responses and disorders, it also seems to be involved in the pathogenesis of the Th1-type skin disease psoriasis. IL-19 therefore represents an exciting new cytokine with immunoregulatory functions.

Keywords: IL-10, IL-20, IL-24, IL-26, Helical cytokine, Asthma, Psoriasis, Th2 response