School of Medicine, Deakin University, Geelong, VIC, Australia.
Institue for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, VIC, Australia.
Front Immunol. 2023 Mar 8;14:1119727. doi: 10.3389/fimmu.2023.1119727. eCollection 2023.
Suppressor of cytokine signaling 3 (SOCS3) is a critical component of the negative feedback regulation that controls signaling by cytokines and other factors thereby ensuring that important processes such as hematopoiesis and inflammation occur at appropriate levels.
To gain further insights into SOCS3 function, the zebrafish gene was investigated through analysis of a knockout line generated using CRISPR/Cas9-mediated genome editing.
Zebrafish knockout embryos displayed elevated numbers of neutrophils during primitive and definitive hematopoiesis but macrophage numbers were not altered. However, the absence of reduced neutrophil functionality but enhanced macrophage responses. Adult knockout zebrafish displayed reduced survival that correlated with an eye pathology involving extensive infiltration of neutrophils and macrophages along with immune cell dysregulation in other tissues.
These findings identify a conserved role for Socs3b in the regulation of neutrophil production and macrophage activation.
细胞因子信号转导抑制因子 3(SOCS3)是一种关键的负反馈调节组件,可控制细胞因子和其他因子的信号转导,从而确保造血和炎症等重要过程在适当的水平发生。
为了更深入地了解 SOCS3 的功能,通过使用 CRISPR/Cas9 介导的基因组编辑生成的敲除系对斑马鱼基因进行了分析。
斑马鱼敲除胚胎在原始和定型造血过程中中性粒细胞数量增加,但巨噬细胞数量没有改变。然而,缺失 SOCS3 并未减少中性粒细胞的功能,但增强了巨噬细胞的反应。成年敲除斑马鱼的存活率降低,这与涉及中性粒细胞和巨噬细胞广泛浸润以及其他组织中免疫细胞失调的眼部病理学有关。
这些发现确定了 Socs3b 在调节中性粒细胞生成和巨噬细胞活化中的保守作用。