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Publication : E-protein-regulated expression of CXCR4 adheres preselection thymocytes to the thymic cortex.

First Author  Kadakia T Year  2019
Journal  J Exp Med Volume  216
Issue  8 Pages  1749-1761
PubMed ID  31201207 Mgi Jnum  J:280067
Mgi Id  MGI:6364252 Doi  10.1084/jem.20182285
Citation  Kadakia T, et al. (2019) E-protein-regulated expression of CXCR4 adheres preselection thymocytes to the thymic cortex. J Exp Med 216(8):1749-1761
abstractText  Preselection thymocytes are normally retained in the thymic cortex, but the mechanisms responsible remain incompletely understood. We now report that deletion of genes encoding the E-protein transcription factors E2A and HEB disorders chemokine receptor expression on developing thymocytes to allow escape of preselection TCR(-)CD8(+) thymocytes into the periphery. We document that CXCR4 expression normally anchors preselection thymocytes to the thymic cortex via interaction with its ligand CXCL12 on cortical thymic epithelial cells, and that disruption of CXCR4-CXCL12 engagements release preselection thymocytes from the thymic cortex. We further document that CXCR4 expression must be extinguished by TCR-mediated positive selection signals to allow migration of TCR-signaled thymocytes out of the thymic cortex into the medulla. Thus, E-protein transcription factors regulate the ordered expression pattern of chemokine receptors on developing thymocytes, and the interaction of the chemokine receptor CXCR4 with its ligand adheres TCR-unsignaled preselection thymocytes to the thymic cortex.
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