Viral Infection Severity Decrease With Extra X Chromosome in Females
Viral infections are known to be more severe in males than females, but the question of why there is a difference in severity remained a mystery until now. The answer to the mystery may lie in an epigenetic regulator that boosts the activity of specialized anti-viral immune cells known as natural killer (NK) cells.
A collaborative team of the University of California, Los Angeles (UCLA) researchers have found that female mouse and human NK cells have an extra copy of an X chromosome-linked gene called UTX. UTX means regulator Ubiquitously transcribed tetratricopeptide repeat on chromosome X. It acts as an epigenetic regulator to boost NK cell anti-viral function while repressing NK cell numbers.
X Chromosome and Sex-Specific Effects in Viral Infection Susceptibility
While it is well-known that males have more NK cells compared to females, we did not understand why the increased number of NK cells was not more protective during viral infections. It turns out that females have more UTX in their NK cells than males, which allows them to fight viral infections more efficiently.‘Female mice with lower UTX expression had more Natural Killer cells which were not as capable of controlling viral infection.’
The researchers noted that this held whether or not the mice had gonads (ovaries in females; testes in males), indicating that the observed trait was not linked to hormones. Furthermore, female mice with lower UTX expression had more NK cells which were not as capable of controlling viral infection. The findings of this experiment are published in the journal Nature Immunology.
This implicates UTX as a critical molecular determinant of sex differences in NK cells. The findings suggest that therapies involving immune responses need to move beyond a "one-size-fits-all" approach and toward a precision medicine model, also known as Extra X Chromosome In Females.
Such approach tailors treatments that take into account people's differences, such as genetics, environment, and other factors that influence health and disease risk. Given the recent excitement about using NK cells in the clinic, researchers need to incorporate sex as a biological factor in treatment decisions and immunotherapy design.
Source: Eurekalert