Functional studies on interleukin 24 in vitro and in vivo

Abstract

FUNCTIONAL STUDIES ON INTERLEUKIN 24 IN VITRO AND IN VIVO

MIAO HE

Thesis under the direction of Professor Peng Liang

Among IL-20 family of cytokines, IL-19, IL-20 and IL-24 can each activate IL20R1/IL-20R2 heterodimeric receptor in vitro; whereas IL-20 and IL-24 can also signal through IL22R1/IL-20R2. The significant receptor sharing among these cytokines based on in vitro biochemical assays with cultured cells thus has raised questions about whether the three cytokines have redundant biological functions in vivo or they may use the same receptors for different biological end points in a tissue specific or temporally regulated manner. However, until now only IL-20 has been proven to play an important role in vivo in the epidermis where both receptors are expressed. In this study, we created IL-24 transgenic mice targeted to the skin. IL-24 transgenic mice exhibit many phenotypes similar to that of IL-20, including neonatal lethality, epidermal hyperplasia and abnormality in keratinocyte differentiation, other than infiltrating macrophages. Moreover, homodimeric IL-20R2 soluble receptor can bind to both IL-20 and IL-24 in vitro with high affinity and potently blocks their ability to bind to cell surface receptors. These results support a redundant role for IL-20 and IL-24 in epidermal functions and a potential therapeutic use of soluble IL-20R2-Fc in autoimmune diseases such as psoriasis where both IL-20 and IL-24 levels are elevated.