Endothelial cells act as gatekeepers for LTβR-dependent thymocyte emigration

Research output: Contribution to journalArticle

External organisations

  • Institute for Immunology and Immunotherapy, College of Medical and Dental Sciences, Medical School, University of Birmingham, Birmingham, England, UK.
  • Department of Microbiology, Immunology and Molecular Genetics, University of Texas School of Medicine, University of Texas Health Science Center, San Antonio, TX.
  • Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, Medical School, University of Birmingham, Birmingham, UK w.e.jenkinson@bham.ac.uk.

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 LTβR, a regulator of thymic microenvironments and thymocyte emigration. Using cell-specific gene targeting, we show that the requirement for LTβR 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 LTβR 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 LTβR in the initiation of thymus emigration that segregates from its control of medulla organization.

Details

Original languageEnglish
Pages (from-to)2984-2993
JournalThe Journal of Experimental Medicine
Volume215
Issue number12
Early online date13 Nov 2018
Publication statusPublished - 3 Dec 2018