Sex Differences in Neutrophil Biology and Autoimmunity

Data shows that there is a difference in susceptibility to infectious diseases and autoimmunity based on whether an individual is biologically female or male. However, the mechanics leading to these differences are still not well understood. A recent paper published in PNAS titled “Sex differences in neutrophil biology modulate response to type I interferons and immunometabolism” helps give insight into some of these differences. 

In this study, researchers collected blood samples from healthy males and females. They focused on neutrophils, the most abundant innate immune cells circulating in the blood. Neutrophils are also known to be associated with the pathogenesis of many autoimmune diseases. So, determining the differences in neutrophils between men and women may help us understand why women are more prone to autoimmune diseases.

Researchers compared the gene expression (how the process of a gene being made into a protein is turned on or off) in neutrophils from male and female participants. They discovered that neutrophils from females exhibit increased responsiveness to interferon, a molecule produced by the immune system. Consequently, females demonstrated elevated levels of interferon-stimulated genes, which can help promote inflammation. Dysregulation in interferon has been implicated in contributing to many autoimmune diseases, so this data supports these findings. Additionally, the researchers noted that these differences in neutrophils are likely due to fluctuations in sex hormones between males and females.

While more research is needed, these differences help us begin to understand why women are more prone to autoimmune diseases than men. The more we understand this mechanism, the more hope there is for developing targeted treatments.

Citations:

Gupta, et al. (2020). Sex differences in neutrophil biology modulate response to type I interferons and immunometabolism. Proceedings of the National Academy of Sciences of the United States of America, 117(28), 16481–16491. https://doi.org/10.1073/pnas.2003603117

Fernandez-Ruiz, R., & Niewold, T. B. (2022). Type I Interferons in Autoimmunity. The Journal of investigative dermatology, 142(3 Pt B), 793–803. https://doi.org/10.1016/j.jid.2021.11.031