Grant: Banting Postdoctoral Fellowship Program

Neutrophils are a type of immune cell in human blood and serve as first responders when we become injured or infected. Previously, neutrophils were thought only to be able to kill microbes and cause inflammation. We discovered in 2017 that neutrophils can also help repair and resolve injuries. One theory to explain this is that there are two different kinds of neutrophils: killing neutrophils and repair neutrophils. However, we do not know how these different kinds of neutrophils are made. Understanding this is important as when neutrophils do not work properly, it can make us vulnerable to severe infections or promote cancer growth. Two possibilities could be that neutrophils are made as killing or repair neutrophils, or they transition from one kind into another. Neutrophils are made inside the bone marrow, and interestingly, we discovered that neutrophils could return to the bone marrow after sensing an injury. We hypothesize that the reason neutrophils return to the bone marrow after an injury is to tell the bone marrow to make repair neutrophils to help heal the injury. To test our hypothesis, we will experimentally injure the livers of mice using a high dose of Tylenol and see if killing neutrophils or repair neutrophils are generated. To do this we have made mice with neutrophils that become fluorescent (light-emitting) when we shine ultraviolet light on them. This will let us track these fluorescent neutrophils using a microscope, allowing us to see where they move and if they transition from killing to repair. We will see if neutrophils go to the bone marrow in these mice, both normally and after liver injury. We will also investigate if repair neutrophils are made following liver injury, and if neutrophils need to go to the bone marrow for repair neutrophils to be made. This research will answer fundamental questions about neutrophils and might lead to new ways to heal injuries and prevent severe infections.