Endothelial cells act as gatekeepers for LTßR-dependent thymocyte emigration.
J Exp Med
; 215(12): 2984-2993, 2018 12 03.
Article
em En
| MEDLINE
| ID: mdl-30425120
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 LTßR, a regulator of thymic microenvironments and thymocyte emigration. Using cell-specific gene targeting, we show that the requirement for LTßR 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 LTßR 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 LTßR in the initiation of thymus emigration that segregates from its control of medulla organization.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Timo
/
Movimento Celular
/
Células Endoteliais
/
Receptor beta de Linfotoxina
/
Timócitos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Reino Unido