How do sex-based differences play a role in our immune system?
It is well known that autoimmune diseases are more likely to affect women than men. For example, women are nine times more likely than men to develop lupus, and two and a half times more likely to develop multiple sclerosis. However, researchers still don't completely understand why women are more at risk of developing autoimmune diseases. Scientists at La Jolla Institute of Immunology (LJI) are currently examining the association between sex hormones, genetics, and environmental factors on the immune system.
LJI Professor Erica Ollmann Saphire, Ph.D., MBA, and LJI Associate Professor Sonia Sharma, Ph.D., are investigating the genetic codes of the XX (female) and XY (male) chromosomes and how they are influenced by hormones such as estrogen and testosterone. These hormones can be used to determine which genes are turned on or off, as well as which genes will be expressed more or less. This also suggests that similar immune cells can exhibit different functions depending on whether they originate from a female or a male.
The X chromosome contains many immune-related genes. Since females have two X chromosomes, they have more immune-related genes at play and can have a stronger immune response in cases where genes from both X chromosomes are activated. Female cells can also vary in terms of which of their two copies of the X chromosome is turned on. This means that women's organs have a complex blend of immune cells that work differently in different tissues.
This greater variety of immune cells can be beneficial in that it sometimes allows women to better fight off infectious diseases. For example, women are shown to be better at fighting off viruses like COVID-19. The downside is that having more immune-related genes from two X chromosomes can potentially predispose women to autoimmune diseases.
Dr. Saphire and Dr. Sharma also emphasized the importance of environmental factors such as chemical exposures and nutrition, which may contribute to the complex interactions of chromosomes and sex hormones. Women and men also seem to have differences in their skin and gut microbiomes. Although more research needs to be done on the combination of genetics, hormones, and environmental factors that increases a woman's risk of autoimmune diseases, this is a foundational step that paves the way for greater understanding and more personalized precision medicine.
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