X chromosome inactivation and maintenance in myeloid cell populations 4578

Abstract Description Sex differences in immune cell composition and function are implicated in contrasting immunologic responses between males and females. Males are more susceptible to bacterial and viral infections, whereas there is a strong female bias in autoimmune disease. While sex hormones contribute to some of these differences, differential gene expression of X chromosome linked immune-related genes also influences this sex bias. The X chromosome contains a number of immune-related genes, and in order to equalize gene expression between sexes, females use X chromosome inactivation (XCI) to generate a transcriptionally silent inactive X chromosome (Xi). Importantly, abnormal X-linked gene expression due to impaired maintenance of the Xi has been demonstrated in adaptive immune cells in patients with autoimmune diseases. While the impact of XCI has been well characterized within the adaptive immune compartment, this has not been well studied in myeloid populations. Here, we examined the maintenance of XCI in murine spleen and bone marrow macrophages and monocytes. In vitro activation of these cells with different toll-like receptor (TLR) agonists resulted in the return of Xist RNA transcripts to the Xi. We also determined the kinetics of Xist RNA localization during in vitro stimulation. We are currently generating mice with a monocyte-specific deletion of Xist (CCR2CreXistfl/fl) to determine whether perturbed XCI maintenance in circulating monocytes contributes to disease. Funding Sources Supported by NIH/NIAID T32AI170501; NIH/NIAID R21AI163596 Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)