Endothelial cells act as gatekeepers for LTβRdependent thymocyte emigration

Kieran D. James, Emilie J. Cosway, Beth Lucas, Andrea J. White, Sonia M. Parnell, Manuela Carvalho-Gaspar, Alexei V Tumanov, Graham Anderson, William E. Jenkinson

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2984-2993
Number of pages10
JournalJournal of Experimental Medicine
Volume215
Issue number12
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

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Emigration and Immigration
Thymocytes
Endothelial Cells
Thymus Gland
Transendothelial and Transepithelial Migration
Gene Targeting
Epithelium
Organizations
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

James, K. D., Cosway, E. J., Lucas, B., White, A. J., Parnell, S. M., Carvalho-Gaspar, M., ... Jenkinson, W. E. (2018). Endothelial cells act as gatekeepers for LTβRdependent thymocyte emigration. Journal of Experimental Medicine, 215(12), 2984-2993. https://doi.org/10.1084/jem.20181345

Endothelial cells act as gatekeepers for LTβRdependent thymocyte emigration. / James, Kieran D.; Cosway, Emilie J.; Lucas, Beth; White, Andrea J.; Parnell, Sonia M.; Carvalho-Gaspar, Manuela; Tumanov, Alexei V; Anderson, Graham; Jenkinson, William E.

In: Journal of Experimental Medicine, Vol. 215, No. 12, 01.12.2018, p. 2984-2993.

Research output: Contribution to journalArticle

James, KD, Cosway, EJ, Lucas, B, White, AJ, Parnell, SM, Carvalho-Gaspar, M, Tumanov, AV, Anderson, G & Jenkinson, WE 2018, 'Endothelial cells act as gatekeepers for LTβRdependent thymocyte emigration', Journal of Experimental Medicine, vol. 215, no. 12, pp. 2984-2993. https://doi.org/10.1084/jem.20181345
James KD, Cosway EJ, Lucas B, White AJ, Parnell SM, Carvalho-Gaspar M et al. Endothelial cells act as gatekeepers for LTβRdependent thymocyte emigration. Journal of Experimental Medicine. 2018 Dec 1;215(12):2984-2993. https://doi.org/10.1084/jem.20181345
James, Kieran D. ; Cosway, Emilie J. ; Lucas, Beth ; White, Andrea J. ; Parnell, Sonia M. ; Carvalho-Gaspar, Manuela ; Tumanov, Alexei V ; Anderson, Graham ; Jenkinson, William E. / Endothelial cells act as gatekeepers for LTβRdependent thymocyte emigration. In: Journal of Experimental Medicine. 2018 ; Vol. 215, No. 12. pp. 2984-2993.
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