Embryonic Neutrophils Perform Adult-Like Immune Functions

Neutrophils, the white blood cells that form part of the body’s first line of defense, have now been shown for the first time to populate many tissues during embryonic development and to perform the same functions as their adult counterparts, according to a new study from the University of Turku, Finland. The findings, published in Nature Communications, suggest a need for further study into the role of embryonic neutrophils in tissue development and in responding to infections in fetuses and newborns. 

Neutrophils are part of the innate immune defense. When inflammation occurs, they rapidly migrate from the bloodstream into tissues to eliminate harmful microbes. Their role is well understood in adults, but remarkably little is known about embryonic neutrophils.

During their studies, the researchers discovered large populations of neutrophils in several developing embryonic tissues.

“We were immediately intrigued. What is the role of these defense cells when the embryo is still safely inside the uterus? The uterus provides an almost sterile environment where there should not yet be any need for rapid defense cells,” said Laura Lintukorpi, co-author of the study.

To dig deeper, the team turned to single-cell RNA sequencing. The technique showed that while embryonic and adult neutrophils expressed genes somewhat differently, both followed a similar path through the major stages of development.

“Embryonic neutrophils were able to perform immune functions typical to adult neutrophils, such as ingesting particles, producing toxic oxygen compounds, and forming web-like structures that trap pathogens outside the cell. Embryonic neutrophils are therefore not merely dormant developing cells, but functionally mature cells,” added first author Julian Hofmann.

According to Hofmann, one of the most interesting findings of the study is the distribution of neutrophils in developing tissues. Because many of the cells are located outside of the blood vessels, they are in direct contact with the developing tissue cells.

“This suggests that embryonic neutrophils may have functions related to tissue development and homeostasis in addition to those related to immune defense,” Hofmann explained.

According to senior author Pia Rantakari, the study is prompting a rethink of how neutrophils and tissues develop in tandem before birth.

“Our findings from experimental models show that neutrophils play a much more active role in developing tissues than was previously thought. Embryonic neutrophils are a functionally competent cell population adapted to a specific stage of development, rather than just immature versions of adult immune cells,” said Rantakari.

Should the same pattern hold true in human tissue, the researchers say it could eventually inform treatments for infections and inflammatory conditions that arise before and shortly after birth.