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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03302009-154357 |
| Date | 21 April 2009 |
| Creators | He, Miao |
| Contributors | Liang, Peng, Chen, Jin |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu//available/etd-03302009-154357/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
Page generated in 0.0115 seconds