Endothelial cells act as gatekeepers for LT?R-dependent thymocyte emigration.

ABSTRACT: The emigration of mature thymocytes from the thymus is critical for establishing peripheral T cell compartments. However, the pathways controlling this process and the timing of egress in relation to postselection developmental stages are poorly defined. Here, we reexamine thymocyte egress and test current and opposing models in relation to the requirement for LT?R, a regulator of thymic microenvironments and thymocyte emigration. Using cell-specific gene targeting, we show that the requirement for LT?R in thymocyte egress is distinct from its control of thymic epithelium and instead maps to expression by endothelial cells. By separating emigration into sequential phases of perivascular space (PVS) entry and transendothelial migration, we reveal a developmentally ordered program of egress where LT?R operates to rate limit access to the PVS. Collectively, we show the process of thymic emigration ensures only the most mature thymocytes leave the thymus and demonstrate a role for LT?R in the initiation of thymus emigration that segregates from its control of medulla organization.

SUBMITTER: James KD 

PROVIDER: S-EPMC6279407 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature