DataSheet_1_Socs3b regulates the development and function of innate immune cells in zebrafish.pdf

IntroductionSuppressor 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.MethodsTo gain further insights into SOCS3 function, the zebrafish socs3b gene was investigated through analysis of a knockout line generated using CRISPR/Cas9-mediated genome editing.ResultsZebrafish socs3b knockout embryos displayed elevated numbers of neutrophils during primitive and definitive hematopoiesis but macrophage numbers were not altered. However, the absence of socs3b reduced neutrophil functionality but enhanced macrophage responses. Adult socs3b 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.DiscussionThese findings identify a conserved role for Socs3b in the regulation of neutrophil production and macrophage activation.

引言：细胞因子信号传导抑制因子3（SOCS3）是负反馈调节的关键组成部分，该调节控制细胞因子及其他因素的信号传导，从而确保如造血和炎症等重要过程在适当的水平发生。方法：为了进一步深入了解SOCS3的功能，通过分析利用CRISPR/Cas9介导的基因组编辑技术产生的敲除系，对斑马鱼的socs3b基因进行了研究。结果：斑马鱼socs3b敲除胚胎在原始和确定性造血过程中表现出中性粒细胞数量增加，但巨噬细胞数量未发生变化。然而，socs3b的缺失降低了中性粒细胞的活性但增强了巨噬细胞的反应。成年socs3b敲除的斑马鱼显示出生存率降低，这与眼病理有关，包括中性粒细胞和巨噬细胞的广泛浸润，以及其他组织中的免疫细胞失调。讨论：这些发现确认了Socs3b在调节中性粒细胞产生和巨噬细胞激活中的保守作用。