Author: Huang, Anliang ; Liu, Haipeng ; Long, Tianzhen ; Liu, Xinyu ; Luo, Guangping ; Liang, Peng ; Zhao, Rongchuan ; Yu, Ruoxuan ; Xu, Yang ; Cui, Jingjing ; Liang, Joshua G. ; Zhou, Hong ; Huang, Xueqin

AbstractTwo heterodimeric receptors consisting of either IL-20R1 or IL-22R1 in complex with a common β receptor subunit IL-20R2 are shared by three of the IL-20 family of cytokines: IL-19, IL-20, and IL-24. These proinflammatory cytokines have been implicated in the pathogenesis of some autoimmune diseases, including rheumatoid arthritis (RA), psoriasis, and atopic dermatitis. Although mAbs against IL-19 and IL-20 have each been shown to modulate disease severity of collagen-induced arthritis in animal models, and anti–IL-20 therapeutic Ab has exhibited some efficacy in the treatment of RA in clinical trials, benefits for a complete blockade of these functionally redundant cytokines remain to be explored. In this report, we show that recombinant human soluble IL-20R2-Fc fusion protein binds to IL-19, IL-20, and IL-24 with similar high affinity and blocks their signaling in vitro. In DBA/1 mouse collagen-induced arthritis model, recombinant human IL-20R2-Fc exhibits comparable efficacy as TNF blocker etanercept in the treatment of established arthritis, whereas the combined use of both biologics manifests little synergistic therapeutic effects. In situ ligand–receptor functional binding analysis shows that a large amount of immune infiltrates expressing high levels of TNFR and IL-20 subfamily cytokines congregate within the inflamed disease tissues. Colocalization experiments reveal that signals from IL-20R2 and TNF transduction pathways seem to converge in macrophages and function in tandem in orchestrating the pathogenesis of RA. Elucidation of this interaction provides a better understanding of cytokine cross-talk in RA and a rationale for more effective biologic therapies that target IL-20R2 instead of individual cytokines from IL-20 family.

01 Jun 2016·Genes & ImmunityQ4 · MEDICINE

Alternative splicing directs two IL-20R2 isoforms and is responsible for the incomplete gene knockout via the exon I ablation

Q4 · MEDICINE

Article

Author: Liu, H ; Yu, R ; Liu, X ; Liang, J G ; Zhou, H ; Xu, Y ; Zhao, R ; Long, T ; Liang, P

Two heterodimeric receptors consisting of interleukin (IL)-20R2 are shared by three of the IL-20 family of cytokines, IL-19, IL-20 and IL-24. Along with IL-22, these cytokines are downstream effectors of IL-23 and have been implicated in keratinocyte functions and the pathogenesis of psoriasis. Surprisingly, whereas knocking out either the IL-23 or IL-22 gene abolished imiquimod-induced psoriatic phenotypes in mice, similar attempt for IL-20R2 had little effect. Here, we report that the apparent disparity may result from a new IL-20R2 isoform encoded by an alternatively spliced transcript which survived the previous attempt for IL-20R2 gene knockout via the exon I deletion.

01 Nov 2010·Biotechnology LettersQ4 · ENGINEERING & TECHNOLOGY

Linear dynamic range for signal detection in fluorescent differential display

Q4 · ENGINEERING & TECHNOLOGY

Article

Author: Blake R. Shester ; Yong-jig Cho ; Jonathan D. Meade ; Jamie C. Walden ; Peng Liang ; Zhen Guo

We have determined the linear dynamic range in signal detection by Fluorescent Differential Display (FDD) using conditionally induced mRNA expression of the p53 tumor-suppressor gene as a control. By serial spiking of p53-induced RNA into that of non-induced RNA, we were able to quantitatively measure up to 100-fold change in p53 mRNA expression level. The linear dynamic range of signal detection per mRNA message was determined to be from 1000 up to 20,000 in fluorescence signal, in which the signals for the majority of mRNAs reside. Thus, FDD can be used to accurately quantify differences in mRNA expression among eukaryotic cells.

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