Murine CCR9, a chemokine receptor for thymus-expressed chemokine that is up-regulated following pre-TCR signaling.
Chemokines are likely to play an important role in regulating the trafficking of developing T cells within the thymus. By using anti-CD3varepsilon treatment of recombinase-activating gene 2 (Rag2-/-) mice to mimic pre-TCR signaling and drive thymocyte development to the double positive stage, we have identified murine GPR-9-6 as a chemokine receptor whose expression is strongly induced following pre-TCR signaling. GPR-9-6 mRNA is present at high levels in the thymus, and by RT-PCR analysis its expression is induced as normal thymocytes undergo the double negative to double positive transition. Furthermore we show that TECK (thymus-expressed chemokine), a chemokine produced by thymic medullary dendritic cells, is a functional ligand for GPR-9-6. TECK specifically induces a calcium flux and chemotaxis of GPR-9-6-transfected cells. In addition, TECK stimulates the migration of normal double positive thymocytes, as well as Rag2-/- thymocytes following anti-CD3varepsilon treatment. Hence, GPR-9-6 has been designated as CC chemokine receptor 9 (CCR9). Our results suggest that TECK delivers signals through CCR9 important for the navigation of developing thymocytes.
Norment
A M
AM
Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle WA 98195, USA. norment@u.washington.edu
Bogatzki
L Y
LY
Gantner
B N
BN
Bevan
M J
MJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D019742:Chemokines, CC / Q000378:metabolism* / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology*; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology*; D013234:Stem Cells / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation / Q000276:immunology*
D000911:Antibodies, Monoclonal; C119309:CC chemokine receptor 9; C491541:Ccl25 protein, mouse; D019742:Chemokines, CC; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; D054388:Receptors, CCR; D019707:Receptors, Chemokine; C064655:V(D)J recombination activating protein 2; C061836:antigen T cell receptor, epsilon chain; D002118:Calcium