IL-24 transgenic mice: in vivo evidence of overlapping functions for IL-20, IL-22, and IL-24 in the epidermis.
IL-20 and IL-24 share two different heterodimeric receptors consisting of either IL-20R1 or IL-22R1 and a common IL-20R2 subunit, whereas IL-22 signals through IL-22R1/IL-10R2. However, until now, only IL-20 and IL-22 have been proven to play important roles in vivo in the epidermis where all four receptor subunits are expressed. In this study, we show that IL-24 transgenic mice manifest many similar phenotypes to that of IL-20 and IL-22, including neonatal lethality, epidermal hyperplasia, and abnormality in keratinocyte differentiation. These results support a largely redundant role in epidermal functions for IL-20, IL-22, and IL-24, which seem to be IL-22R1 dependent. Moreover, we show that IL-24 transgenic mice exhibit infiltrating macrophages in the dermis with concomitant increases in MCP-1 production from both keratinocytes in the epidermis and immune infiltrates in the adjacent dermal layer below. Furthermore, we demonstrate that the homodimeric IL-20R2 soluble receptor is a potent blocker for IL-24 and can be used to further dissect the crosstalk among the IL-20 family of cytokines in normal development as well as in autoimmune diseases.
He
Miao
M
Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Liang
Peng
P
D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005804:Genes, Lethal; D005807:Genes, Overlapping / Q000276:immunology*; D006801:Humans; D006965:Hyperplasia; D016130:Immunophenotyping; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015603:Keratinocytes / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000097043:Interleukin-22; D000099180:Interleukin-24
D007378:Interleukins; D011993:Recombinant Fusion Proteins; D000097043:Interleukin-22; D000099180:Interleukin-24; C422042:interleukin 20