TECK (thymus-expressed chemokine), a recently described CC chemokine expressed in thymus and small intestine, was found to mediate chemotaxis of human G protein–coupled receptor GPR-9-6/L1.2 transfectants. This activity was blocked by anti–GPR-9-6 monoclonal antibody (mAb) 3C3. GPR-9-6 is expressed on a subset of memory α4β7high intestinal trafficking CD4 and CD8 lymphocytes. In addition, all intestinal lamina propria and intraepithelial lymphocytes express GPR-9-6. In contrast, GPR-9-6 is not displayed on cutaneous lymphocyte antigen–positive (CLA+) memory CD4 and CD8 lymphocytes, which traffic to skin inflammatory sites, or on other systemic α4β7−CLA− memory CD4/CD8 lymphocytes. The majority of thymocytes also express GPR-9-6, but natural killer cells, monocytes, eosinophils, basophils, and neutrophils are GPR-9-6 negative. Transcripts of GPR-9-6 and TECK are present in both small intestine and thymus. Importantly, the expression profile of GPR-9-6 correlates with migration to TECK of blood T lymphocytes and thymocytes. As migration of these cells is blocked by anti–GPR-9-6 mAb 3C3, we conclude that GPR-9-6 is the principal chemokine receptor for TECK. In agreement with the nomenclature rules for chemokine receptors, we propose the designation CCR-9 for GPR-9-6. The selective expression of TECK and GPR-9-6 in thymus and small intestine implies a dual role for GPR-9-6/CCR-9, both in T cell development and the mucosal immune response.
Human G Protein–Coupled Receptor Gpr-9-6/Cc Chemokine Receptor 9 Is Selectively Expressed on Intestinal Homing T Lymphocytes, Mucosal Lymphocytes, and Thymocytes and Is Required for Thymus-Expressed Chemokine–Mediated Chemotaxis
Abbreviations used in this paper: CLA, cutaneous lymphocyte–associated antigen; G3PDH, glyceraldehyde 3-phosphate dehydrogenase; GPR, human G protein–coupled receptor; HEV, high endothelial venule; IEL, intraepithelial lymphocyte; IP-10, IFN-γ–inducible 10-kD protein; I-TAC, IFN-inducible T cell α chemoattractant; LPL, lamina propria lymphocyte; MCP, monocyte chemoattractant protein; MDC, macrophage-derived chemokine; MIG, monokine induced by IFN-γ; MIP, macrophage inflammatory protein; RANTES, regulated upon activation, normal T cell expressed and secreted protein; SDF, stromal cell–derived factor; TARC, thymus and activation-regulated chemokine; TECK, thymus-expressed chemokine.
B.A. Zabel and W.W. Agace contributed equally to this work.
Brian A. Zabel, William W. Agace, James J. Campbell, Heidi M. Heath, David Parent, Arthur I. Roberts, Ellen C. Ebert, Nasim Kassam, Shixin Qin, Maria Zovko, Gregory J. LaRosa, Li-Li Yang, Dulce Soler, Eugene C. Butcher, Paul D. Ponath, Christina M. Parker, David P. Andrew; Human G Protein–Coupled Receptor Gpr-9-6/Cc Chemokine Receptor 9 Is Selectively Expressed on Intestinal Homing T Lymphocytes, Mucosal Lymphocytes, and Thymocytes and Is Required for Thymus-Expressed Chemokine–Mediated Chemotaxis. J Exp Med 1 November 1999; 190 (9): 1241–1256. doi: https://doi.org/10.1084/jem.190.9.1241
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