GSE107981
Effector and regulatory T cells roll at high shear stress by inducible tether and sling formation
The adaptive immune response involves T cell differentiation and migration to  sites of inflammation. T cell trafficking is initiated by tethering and rolling on  inflamed endothelium. Tethers and slings, discovered in neutrophils, facilitate  cell rolling at high shear stress. Here we demonstrate that PSGL-1 binding to  P- or E-selectins and the ability to form tethers and slings during rolling are  highly inducible in T-helper-1 (Th1), Th17 and regulatory (Treg), but less in  Th2 cells. In vivo, endogenous Tregs rolled stably in cremaster venules at  physiological shear stress. Quantitative dynamic footprinting nanoscopy of  Th1, Th17 and Tregs uncovered the formation of multiple tethers. Importantly,  human Th1 cells also showed tethers and slings. RNA-Seq revealed that  sling-forming cells induced genetic pathways related to cell motility. We  conclude that differentiated CD4 T cells stabilize rolling by inducible tether  and sling formation. These phenotypic changes approximate the adhesion  phenotype of neutrophils and support CD4 T cell access to sites of  inflammation in non-lymphoid tissues. Overall design: Examination of mRNA expression profiles contributing to Tethers and Slings formation in CD4 T cell subsets by RNA-seq deep sequencing analysis by Hiseq 4000