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, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, 201306, China; National Demonstration Center for Experimental Fisheries Science Education, University, Shanghai, 201306, China.
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, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, 201306, China; National Demonstration Center for Experimental Fisheries Science Education, University, Shanghai, 201306, China; Department of Fish Diseases, Faculty of Veterinary Medicine, Aswan University, Sahari, Airport Way, 81528, Egypt.
Fish Shellfish Immunol. 2023 Jan;132:108445. doi: 10.1016/j.fsi.2022.11.033. Epub 2022 Nov 19.
IL-20 is a pleiotropic cytokine that belongs to the IL-10 family and has a variety of biological functions in tissue homeostasis and regulation of host immune defenses. It signals through a heterodimeric receptor composed of a subunit with a long intracellular domain (R1 type receptor) and a subunit with a short intracellular domain (R2 type receptor). In this study, the R1 type receptor (CiIL-20R1/CRFB8) and the R2 type receptor (CiIL-20R2/CRFB16) were identified in grass carp Ctenopharyngodon idella. Expression analysis revealed that IL-20R2 was highly expressed in the gills and skin in healthy fish. Infection with Flavobacterium columnare resulted in the downregulation of both receptors in the gill at 48 and 72 h, whilst infection with grass carp reovirus induced their expression in the head kidney and spleen at 72 h. In the primary head kidney leucocytes, the expression levels of IL-20R1 and IL-20R2 were decreased after stimulation with 250 ng/mL IL-1β but not affected by IFN-γ. Co-immunoprecipitation analysis showed that CiIL-20R2/CRFB16 but not CiIL-20R1/CRFB8 bound to CiIL-20L. Furthermore, it was shown that CiIL-20R1/CRFB8 was responsible for activating the phosphorylation of STAT3, whilst CiIL-20R2/CRFB16 was not involved. Structural modeling analysis showed that key residues involved in the interaction between IL-20 and receptors were highly conserved between grass carp and humans, suggesting that the signal transduction and functions of IL-20/IL-20R axis are evolutionarily conserved.
白细胞介素-20（IL-20）是一种多功能细胞因子，属于白细胞介素 10 家族，在组织稳态和宿主免疫防御调节中具有多种生物学功能。它通过由具有长细胞内结构域的亚基（R1 型受体）和具有短细胞内结构域的亚基（R2 型受体）组成的异二聚体受体信号传导。在这项研究中，草鱼（Ctenopharyngodon idella）中鉴定出了 R1 型受体（CiIL-20R1/CRFB8）和 R2 型受体（CiIL-20R2/CRFB16）。表达分析显示，IL-20R2 在健康鱼类的鳃和皮肤中高表达。感染柱状屈挠杆菌（Flavobacterium columnare）导致 48 和 72 小时时在鳃中两种受体下调，而感染草鱼呼肠孤病毒（grass carp reovirus）诱导其在头肾和脾脏中在 72 小时时表达。在原头肾白细胞中，用 250ng/mL 的 IL-1β 刺激后，IL-20R1 和 IL-20R2 的表达水平降低，但不受 IFN-γ影响。免疫共沉淀分析表明，CiIL-20R2/CRFB16 而不是 CiIL-20R1/CRFB8 与 CiIL-20L 结合。此外，结果表明 CiIL-20R1/CRFB8 负责激活 STAT3 的磷酸化，而 CiIL-20R2/CRFB16 不参与。结构建模分析表明，IL-20 与受体相互作用的关键残基在草鱼和人类之间高度保守，表明 IL-20/IL-20R 轴的信号转导和功能在进化上是保守的。
