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PMID:10623805

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Citation

Norment, AM, Bogatzki, LY, Gantner, BN and Bevan, MJ (2000) Murine CCR9, a chemokine receptor for thymus-expressed chemokine that is up-regulated following pre-TCR signaling. J. Immunol. 164:639-48

Abstract

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.

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PubMed

Keywords

Animals; Antibodies, Monoclonal/pharmacology; Calcium/metabolism; Cell Differentiation/genetics; Cell Differentiation/immunology; Cell Line; Cell Movement/immunology; Chemokines, CC/metabolism; Chemokines, CC/physiology; Chemotaxis, Leukocyte/immunology; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/genetics; Mice; Mice, Inbred C57BL; Mice, Transgenic; Receptors, Antigen, T-Cell/immunology; Receptors, Antigen, T-Cell/physiology; Receptors, CCR; Receptors, Chemokine/biosynthesis; Receptors, Chemokine/genetics; Signal Transduction/immunology; Stem Cells/metabolism; T-Lymphocyte Subsets/immunology; T-Lymphocyte Subsets/metabolism; Thymus Gland/cytology; Thymus Gland/metabolism; Transfection; Up-Regulation/immunology

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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