Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China; International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China.
Fish Shellfish Immunol. 2019 Apr;87:254-264. doi: 10.1016/j.fsi.2019.01.009. Epub 2019 Jan 8.
Interleukin (IL)-4 and IL-13 are T helper 2 (Th2) cytokines with pleiotropic functions. IL-4 interacts with two receptors consisting of IL-4Rα/γ chain receptor (γC) and IL-4Rα/IL-13Rα1. In contrast, IL-13 binds to IL-13Rα2 but also shares the receptor complex containing IL-4Rα/IL-13Rα1. In fish, two IL-4/13 homologs have been identified but their phylogenetic relationships with IL-4 and IL-13 are ambiguous. In this study, we identified six putative IL-4/13 receptor homologs in grass carp, including γC1, γC2, IL-4Rα1, IL-13Rα1, IL-13Rα2 and a soluble form of IL-4Rα2. Comparative sequence analyses revealed that these receptors possess conserved characteristic domains and the genes encoding them share conserved gene synteny with their human counterparts. All six receptors contain a cytokine binding homology domain (CHD) and two fibronectin type Ⅲ (FNⅢ) like domains, with IL-13Rα1 and IL-13Rα2 harbouring an extra Ig-like domain preceding the CHD domain. Interestingly, grass carp IL-13Rα1 and IL-13Rα2 lack the characteristic WSXWS motif, a typical feature of mammalian type I cytokine receptors. The IL-4/13 receptor genes are differentially expressed in tissues and primary leukocytes of head kidney and can be modulated by Flavobacterium cloumnare (F. cloumnare), suggesting they are involved in immune response against F. cloumnare infection.
白细胞介素 (IL)-4 和 IL-13 是 T 辅助 2 (Th2) 细胞因子,具有多种功能。IL-4 与由 IL-4Rα/γ 链受体 (γC) 和 IL-4Rα/IL-13Rα1 组成的两种受体相互作用。相比之下,IL-13 与 IL-13Rα2 结合,但也与包含 IL-4Rα/IL-13Rα1 的受体复合物共享。在鱼类中,已经鉴定出两种 IL-4/13 同源物,但它们与 IL-4 和 IL-13 的系统发育关系尚不清楚。在这项研究中,我们在草鱼中鉴定了六个推定的 IL-4/13 受体同源物,包括 γC1、γC2、IL-4Rα1、IL-13Rα1、IL-13Rα2 和 IL-4Rα2 的可溶性形式。比较序列分析表明,这些受体具有保守的特征结构域,编码它们的基因与人类对应物具有保守的基因同线性。所有六个受体都包含细胞因子结合同源结构域 (CHD) 和两个纤维连接蛋白 III (FNⅢ) 样结构域,其中 IL-13Rα1 和 IL-13Rα2 在 CHD 结构域之前含有额外的 Ig 样结构域。有趣的是,草鱼 IL-13Rα1 和 IL-13Rα2 缺乏典型的 WSXWS 基序,这是哺乳动物 I 型细胞因子受体的一个典型特征。IL-4/13 受体基因在组织和头肾的原代白细胞中差异表达,并可被 Flavobacterium cloumnare (F. cloumnare) 调节,表明它们参与了对 F. cloumnare 感染的免疫反应。