Du Linyong, Feng Shiyu, Yin Licheng, Wang Xinyan, Zhang Anying, Yang Kun, Zhou Hong
School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
Dev Comp Immunol. 2015 Jul;51(1):202-11. doi: 10.1016/j.dci.2015.03.014. Epub 2015 Apr 3.
In mammals, IL-17A and IL-17F are hallmark cytokines of Th17 cells which act significant roles in eradicating extracellular pathogens. IL-17A and IL-17F homologs nominated as IL-17A/F1-3 have been revealed in fish and their functions remain largely undefined. Here we identified and characterized grass carp IL-17A/F1 (gcIL-17A/F1) in fish immune system. In this regard, both tissue distribution and inductive expression of gcIL-17A/F1 indicated its possible involvement in immune response. Moreover, recombinant gcIL-17A/F1 (rgcIL-17A/F1) was prepared and displayed an ability to enhance pro-inflammatory cytokines (IL-1β, TNF-α and IL-6) mRNA expression in head kidney leukocytes. It is suggestive of that gcIL-17A/F1 may act as a proinflammatory cytokine in fish immunity. Besides, rgcIL-17A/F1 induced gene expression and protein release of grass carp chemokine CXCL-8 (gcCXCL-8) in head kidney cells (HKCs), probably via NF-κB, p38 and Erk1/2 pathways. In particular, culture medium from the HKCs treated by rgcIL-17A/F1 could stimulate peripheral blood leukocytes migration and immunoneutralization of endogenous gcCXCL-8 could partially attenuate this stimulation, suggesting that rgcIL-17A/F1 could recruit immune cells through producing gcCXCL-8 as mammalian IL-17 A and F. Taken together, we not only identified the pro-inflammatory role of gcIL-17A/F1 in host defense, but also provided the basis for clarifying Th17 cells in teleost.
在哺乳动物中，白细胞介素-17A（IL-17A）和白细胞介素-17F（IL-17F）是辅助性T细胞17（Th17）细胞的标志性细胞因子，在清除细胞外病原体中发挥重要作用。在鱼类中已发现了被命名为IL-17A/F1-3的IL-17A和IL-17F同源物，但其功能在很大程度上仍不明确。在此，我们在鱼类免疫系统中鉴定并表征了草鱼IL-17A/F1（gcIL-17A/F1）。在这方面，gcIL-17A/F1的组织分布和诱导表达均表明其可能参与免疫反应。此外，制备了重组gcIL-17A/F1（rgcIL-17A/F1），其显示出增强头肾白细胞中促炎细胞因子（IL-1β、肿瘤坏死因子-α和IL-6）mRNA表达的能力。这表明gcIL-17A/F1可能在鱼类免疫中作为一种促炎细胞因子发挥作用。此外，rgcIL-17A/F1诱导头肾细胞（HKCs）中草鱼趋化因子CXCL-8（gcCXCL-8）的基因表达和蛋白释放，可能是通过核因子κB（NF-κB）、p38和细胞外信号调节激酶1/2（Erk1/2）途径。特别地，rgcIL-17A/F1处理的HKCs的培养基可刺激外周血白细胞迁移，内源性gcCXCL-8的免疫中和可部分减弱这种刺激，这表明rgcIL-17A/F1可像哺乳动物的IL-17A和F一样通过产生gcCXCL-8来募集免疫细胞。综上所述，我们不仅鉴定了gcIL-17A/F1在宿主防御中的促炎作用，还为阐明硬骨鱼中的Th17细胞提供了依据。
