The role of UGCG in CD8+ T cells 3893

Abstract Description Glycosphingolipids (GSLs) are ubiquitous membrane components that are integral for selective transport and protein trafficking. UDP-glucose ceramide glycosyltransferase (UGCG) catalyzes the first glycosylation step to generate glucosylceramide (GlcCer), a precursor for GSLs. There are 400 different species of GSLs, and changes in expression of some of these lipids have been observed in T cells. However, there has been a lack of genetic models to study how GSLs impact T cell biology. Therefore, we explored the impact of loss of Ugcg in CD8+ T cells. CD8+ T cells are adaptive lymphocytes that are essential for immune regulation, homeostasis, and forming immunological memory during inflammatory reactions. To determine how GSLs regulate CD8+ T cells, we generated CD4cre-Ugcg mice to delete Ugcg expression in T cells. Flow cytometry analysis revealed upregulation of CCR7 expression in CD8+ T cells in conditional knockout mice. CCR7 is a chemokine receptor that mobilizes naive and memory T cells into secondary lymphoid organs, suggesting increased CD8+ T cell retention in cKO mice. We also infected mice with LCMV and observed fewer antigen-specific CD8+ T cells. Further investigation is underway to determine if upregulation of CCR7 impairs T cell trafficking into tumors, and explore the mechanism of how GSLs regulate expansion of activated T cells. Topic Categories Cytokines and Chemokines and Their Receptors (CCR)