CD209同源基因在斑马鱼中的鉴定及功能表征  

Identification and functional characterization of CD209 homologous genes in zebrafish

作　　者：杨晓君 黄振瀚 刘伟 张文清 黄志斌 Xiaojun Yang;Zhenhan Huang;Wei Liu;Wenqing Zhang;Zhibin Huang(Innovation Centre of Ministry of Education for Development and Diseases,School of Medicine,South China University of Technology,Guangzhou 510006,China)

机构地区：[1]华南理工大学医学院,教育部发育与疾病医药基础研究创新中心,广州510006

出　　处：《遗传》2024年第11期947-957,共11页Hereditas（Beijing)

基　　金：国家自然科学基金项目(编号:32170830);广东省自然科学基金项目(编号:2021A1515010422)资助。

摘　　要：先天免疫反应在维持机体稳态中扮演关键角色,其启动与先天免疫细胞表面的模式识别受体或损伤相关分子密切相关。CD209作为巨噬细胞或树突状细胞表面的模式识别受体,在免疫功能中具有重要作用。然而,目前尚不清楚CD209在体内对先天免疫细胞如巨噬细胞、中性粒细胞的影响。本研究通过多序列比对和系统进化树构建,发现斑马鱼(Danio rerio)中存在3个与人CD209同源的基因,分别是cd209(Ensembl ID:ENSDARG00000029461)、zgc:174904(Ensembl ID:ENSDARG00000059049)和si:dkey-187i8.2(Ensembl ID:ENSDARG00000096624)。与Ensembl数据库中的cd209和si:dkey-187i8.2基因相比,zgc:174904在序列上与人CD209更为相似。通过整体原位杂交和荧光共定位实验,本研究发现zgc:174904主要在巨噬细胞表达。进一步通过morpholino敲低实验,结果显示,敲低zgc:174904会导致M1型巨噬细胞相关基因的上调以及成熟中性粒细胞数量的减少,表明zgc:174904在功能上与CD209更为相似。本研究结果不仅揭示了CD209在调控巨噬细胞功能和中性粒细胞发育中的潜在作用,还为先天免疫机制的研究提供了重要的线索。Innate immune responses play a crucial role in maintaining homeostasis,their initiation closely related to pattern recognition receptors or damage-associated molecules on the surface of innate immune cells.CD209,a pattern recognition receptor on the surface of macrophages or dendritic cells,plays an important role in immune functions.However,the impact of CD209 on innate immune cells such as macrophages or neutrophils in vivo remains unclear.In this study,through multiple sequence alignment and phylogenetic tree construction,three genes homologous to human CD209 were found in zebrafish.These are cd209(Ensembl ID:ENSDARG00000029461),zgc:174904(Ensembl ID:ENSDARG00000059049)and si:dkey-187I7.2(Ensembl ID:ENSDARG00000096624).Compared to the cd209 and si:dkey-187i8.2 genes in the Ensembl database,zgc:174904 is more similar to human CD209 in sequence.Using whole-mount in situ hybridization and fluorescence co-localization experiments,it was found that zgc:174904 is mainly expressed in macrophages.Further morpholino knockdown experiments showed that knocking down zgc:174904 leads to an upregulation of M1-type macrophage-related genes and a decrease in the number of mature neutrophils,indicating that zgc:174904 is functionally more similar to CD209.These findings not only reveal the potential role of CD209 in regulating macrophage function and neutrophil development but also provide significant insights for research into the mechanisms of innate immunity.

关 键 词：先天性免疫 CD209 巨噬细胞极化 粒细胞 斑马鱼 

分 类 号：R392[医药卫生—免疫学]