Truong Anh Duc, Hoang Cong Thanh, Hong Yeojin, Lee Janggeun, Lee Kyungbaek, Lillehoj Hyun S, Hong Yeong Ho
Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea; National Institute of Veterinary Research, 86 Truong Chinh, Dong Da, Hanoi, Viet Nam.
Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea.
Mol Immunol. 2017 Dec;92:54-67. doi: 10.1016/j.molimm.2017.09.019. Epub 2017 Oct 16.
This study represents the first description of the cloning of chicken IL-23p19 (ChIL-23α) and the function of the IL-23 complex in birds. Multiple alignment of ChIL-23α with other known IL-23α amino acid sequences revealed regions of amino acid conservation. The homologies of ChIL-23α, IL-12p35, and similar mammalian subunits ranged between 26% and 42%. ChIL-23α consisted of four exons and three introns; similar to those in humans and mice, and limited conservation of synteny between the human and chicken genomes was observed. Using bioinformatics tools, we identified the NF-κB, C/EBPα-β, c-Jun, c-Rel, AP-1, GATA-1, and ER promoter sites in ChIL-23α. Moreover, IL-23α mRNA was more highly expressed than IL-12p40 and IL-12p35 mRNA in several organs of chickens infected with Salmonella. In addition, ChIL-23 complex are associated with IL-23R, IL-12Rβ1 receptors; activate the JAK2/TYK2, STAT1/3, SOCS1 genes, and induced proinflammatory cytokines in immune cells. Collectively, these results indicate that ChIL-23 is a member of the IL-12 family, has proinflammatory properties related to IL-23R and IL-12Rβ1 receptor expression, and activates the JAK/STAT signaling pathway that results in the interaction of ChIL-23α with ChIL-12p40 to form the novel ChIL-23 complex. Our results provide novel insights into the regulation of immunity, inflammation, and immunopathology.
本研究首次描述了鸡白细胞介素-23 p19（ChIL-23α）的克隆以及白细胞介素-23复合物在禽类中的功能。ChIL-23α与其他已知白细胞介素-23α氨基酸序列的多重比对揭示了氨基酸保守区域。ChIL-23α、白细胞介素-12 p35以及类似的哺乳动物亚基之间的同源性在26%至42%之间。ChIL-23α由四个外显子和三个内含子组成；与人类和小鼠中的情况相似，并且观察到人类和鸡基因组之间有限的同线性保守性。使用生物信息学工具，我们在ChIL-23α中鉴定出了核因子κB、C/EBPα-β、c-Jun、c-Rel、活化蛋白-1、GATA-1和雌激素受体启动子位点。此外，在感染沙门氏菌的鸡的多个器官中，白细胞介素-23α mRNA的表达高于白细胞介素-12 p40和白细胞介素-12 p35 mRNA。另外，ChIL-23复合物与白细胞介素-23受体、白细胞介素-12受体β1相关；激活JAK2/TYK2、信号转导和转录激活因子1/3、细胞因子信号转导抑制因子1基因，并在免疫细胞中诱导促炎细胞因子。总体而言，这些结果表明ChIL-23是白细胞介素-12家族的成员，具有与白细胞介素-23受体和白细胞介素-12受体β1表达相关的促炎特性，并激活JAK/信号转导和转录激活因子信号通路，导致ChIL-23α与白细胞介素-12 p40相互作用形成新的ChIL-23复合物。我们的结果为免疫、炎症和免疫病理学的调控提供了新的见解。
