X chromosome inactivation (XCI) is initiated at random by the lncRNA Xist, leading to the deposition of silencing epigenetic modifications on the Xi during development that remain stable throughout the organism’s life. Thus, female mammals are mosaic for which X chromosome is active. Lymphocytes undergo a unique pattern of “dynamic XCI”, where Xist RNA foci and silencing marks are absent in mature naïve lymphocytes and relocalize upon activation.

Many autoimmune diseases exhibit a female bias, and the X chromosome is enriched in immune related genes. Xist mislocalization to the Xi in immune cells has been associated with autoimmunity in humans and lupus like disease in mice. Certain viral infections have also been associated with the incidence of autoantibodies, which are markers for autoimmune disease.

In this experiment, we infected female CD4+ T cell Xist cKO mice with influenza and found that cKO mice were protected as they lost less weight than their wild type counterparts. However, the knockout did not predispose mice to developing higher titers of anti dsDNA autoantibodies. Influenza infection was associated with slightly elevated anti dsDNA autoantibody titers. Further study must elucidate the reason behind why the cKO mice are protected and consider alternatives to influenza infection.