E-protein–regulated expression of CXCR4 adheres preselection thymocytes to the thymic cortex
Autor: | Jan Wisniewski, Terry I. Guinter, John H. Kehrl, Yuan Zhuang, Tejas Kadakia, Xuguang Tai, Il-Young Hwang, Michael J. Kruhlak, Sumedha Roy, Alfred Singer, Amala Alag |
---|---|
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Receptors CXCR4 CD8 Antigens Transgene Immunology Receptors Antigen T-Cell Mice Transgenic Thymus Gland Biology CXCR4 Article Mice 03 medical and health sciences Chemokine receptor 0302 clinical medicine Basic Helix-Loop-Helix Transcription Factors Animals Humans Immunology and Allergy Receptor Gene Transcription factor Research Articles Medulla Thymocytes Lymphopoiesis Cell Differentiation Epithelial Cells Ligand (biochemistry) Chemokine CXCL12 Cell biology Mice Inbred C57BL 030104 developmental biology 030220 oncology & carcinogenesis psychological phenomena and processes Signal Transduction |
Zdroj: | The Journal of Experimental Medicine |
ISSN: | 1540-9538 0022-1007 |
Popis: | The E-protein transcription factors E2A and HEB regulate thymocyte expression of the chemokine receptor CXCR4 to retain preselection thymocytes in the thymic cortex. TCR-mediated positive selection signals extinguish CXCR4 expression to allow positively selected thymocytes to migrate from the cortex into the thymic medulla. 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. Graphical Abstract |
Databáze: | OpenAIRE |
Externí odkaz: |