An integral T cell pathway helps regulate female gene expression

By: Erica Moser Date: Oct 10, 2024

Microscopic view of an X chromosome — Image: iStock/Alllex

The well-established existence of sex differences in immune responses, including immune responses driven by T cells, cuts both ways. Females tend to have a stronger immune response to pathogens, yet most patients who have autoimmune diseases involving dysregulated T cells are female.

In the School of Veterinary Medicine, Montserrat Anguera and her lab have been interested in how the X chromosome is involved in these processes. In certain female mammals, gene expression is regulated through X chromosome inactivation, where one of the two X chromosomes is silenced. This process is initiated and maintained by expression of Xist RNA, a long noncoding RNA molecule, from the inactive X chromosome.

Previous work from the Anguera Lab showed that unstimulated T cells lack Xist RNA and other modifications on the inactive X chromosome, but when T cells are activated with an antigen the Xist RNA and epigenetic marks return. She and collaborators wondered: What signals are necessary for the Xist RNA to return? And how much of the inactive X chromosome is silenced in T cells?

About Penn Vet

Ranked among the top ten veterinary schools worldwide, the University of Pennsylvania School of Veterinary Medicine (Penn Vet) is a global leader in veterinary education, research, and clinical care. Founded in 1884, Penn Vet is the first veterinary school developed in association with a medical school. The school is a proud member of the One Health initiative, linking human, animal, and environmental health.

Penn Vet serves a diverse population of animals at its two campuses, which include extensive diagnostic and research laboratories. Ryan Hospital in Philadelphia provides care for dogs, cats, and other domestic/companion animals, handling more than 34,600 patient visits a year. New Bolton Center, Penn Vet’s large-animal hospital on nearly 700 acres in rural Kennett Square, PA, cares for horses and livestock/farm animals. The hospital handles more than 6,200 patient visits a year, while our Field Services have gone out on more than 5,500 farm service calls, treating some 18,700 patients at local farms. In addition, New Bolton Center’s campus includes a swine center, working dairy, and poultry unit that provide valuable research for the agriculture industry.