Protein 4.1R regulates neutrophil function through the JAK2/STAT3 signaling pathway

Abstract

AbstractNeutrophils are important components of innate immunity in the blood. They are the body's first line of defense against microbial pathogens, especially when suppurative bacteria invade. Since its function can be both beneficial and harmful to the pathogen and the surrounding host tissues, its functions must be tightly regulated. First discovered in red blood cells, the 4.1R protein is a membrane skeleton protein that plays an important role in regulating the deformation and stability of the membrane. Many lines of evidence suggest that 4.1R has the ability to regulate cellular pathways in a variety of immune cells, but its function in neutrophils has not yet been reported. Here, we investigated the function of 4.1R in neutrophils using 4.1R−/−mice. Our results showed that the chemotactic function, phagocytic function, ROS production ability, and the secretion of inflammatory factors were increased in the 4.1R−/−neutrophils. Furthermore, results fromin vivoexperiments demonstrated that 4.1R−/−mice recruited more neutrophils, secreted higher levels of inflammatory cytokines, and had a shorter life-span. Further mechanistic evaluation revealed that the protein phosphorylation of JAK2/STAT3 was increased in the 4.1R knockout neutrophils after their stimulation and activation. In summary, the expression of 4.1R protein has an important negative regulatory effect on neutrophil function, which may be mediated through the JAK2/STAT3 signaling pathway.