Suppression of human and mouse Th17 differentiation and autoimmunity by an endogenous Interleukin 23 receptor cytokine-binding homology region
Suppression of human and mouse Th17 differentiation and autoimmunity by an endogenous Interleukin 23 receptor cytokine-binding homology region
复制标题
内源性白细胞介素 23 受体细胞因子结合同源区抑制人和小鼠 Th17 分化和自身免疫
DOI：
10.1016/j.biocel.2014.09.019
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发表时间：
2014-10-01
影响因子：
4
通讯作者：
Yao, Wen Bing
中科院分区：
文献类型：
--
作者：
Guo, Wei;Luo, Cheng;Yao, Wen Bing
T-helper 17 (Th17) cells, a recently identified CD4+ T subset with a unique characteristic to produce Interleukin-17 (IL-17), are critical for the development of autoimmune diseases such as multiple sclerosis, in which IL-23 plays an important role in the differentiation of Th17 cells through IL-23/IL-23-receptor/STAT3 pathway. Previously, soluble recombinant human IL-23 receptor cytokine-binding homology region (hIL23R-CHR) was constructed in our laboratory to neutralize IL-23 and inhibit murine Th17 development in vitro. Herein we present that hIL23R-CHR could inhibit both differentiation and function of human/murine Th17 cells. The present in vivo study further demonstrated that hIL23R-CHR inhibited murine Th17 cell development by down regulating IL-17 gene expression and protected mice against the development of experimental autoimmune encephalomyelitis (EAE) through suppression of CNS inflammation and pro-inflammatory cytokine production. In addition to the in vitro inhibition of human Th17 cells in a dose-dependent manner, the antagonizing effect of hIL23R-CHR was confirmed by reduced levels of IL-23 in both blood and brain of EAE mice and STAT3 phosphorylation in vivo. Taken together, our data demonstrated that hIL23R-CHR could be an effective and specific immunosuppressive molecule for the treatment of Th17-related autoimmune diseases. (C) 2014 Elsevier Ltd. All rights reserved.
