The immune system is not a one-size-fits-all defense; it varies significantly between sexes, influencing susceptibility to diseases such as autoimmune disorders, cancer, and infections. Women are generally more prone to autoimmune diseases, while men exhibit higher rates of cancer and increased sensitivity to infections—patterns that can be traced back to intrinsic differences in their immune systems. Understanding the drivers, consequences, and modulation potential of these differences is critical for developing effective, sex-specific treatments.

A male-centric bias has long dominated biological research, particularly in drug clinical trials. This bias often results in diminished therapeutic responses or increased adverse events in women. While strides have been made since the NIH mandated the inclusion of women in clinical trials in 1993, many non-human immunological studies still overlook the importance of sex as a variable. By thoroughly investigating these “natural differences” between sexes and uncovering their underlying causes and consequences, we can significantly enhance our understanding of sex-biased diseases and potentially uncover new therapeutic avenues for improved health outcomes.

Scientists only recently identified an immune cell population called ILC1 (Innate Lymphoid Cell Type 1). ILC1s have quickly emerged as a key contributor in early viral responses, tumor control, and autoimmune disorders. ILC1s are distinguished by their ability to produce potent and rapid cytokine responses. Their cytotoxic capabilities enable them to effectively eliminate cancerous and infected cells, positioning them at the forefront of sex-based immunology research. I hypothesize that ILC1s will exhibit distinct functions and phenotypes in males and females, and that these variations may significantly influence the observed differences in immune responses between the sexes. I will examine how ILC1s respond differently to viral infections in male and female mice using cytomegalovirus (CMV), a virus that affects more than 50 percent of Americans. I believe that this approach will help us better understand ILC1s and their roles in the differences in immune responses between sexes, leading to more effective and personalized treatment options.