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Cutting Edge: Identification of the Orphan Chemokine Receptor GPR-9-6 as CCR9, the Receptor for the Chemokine TECK¹

Ángel Zaballos^*, Julio Gutiérrez^*, Rosa Varona^*, Carlos Ardavín and Gabriel Márquez^2,*

^* Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología, Universidad Autónoma de Madrid, Madrid, Spain; and Departamento de Biología Celular, Facultad de Biología, Universidad Complutense, Madrid, Spain

	Abstract

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Thymus-expressed chemokine (TECK) has been reported to chemoattract dendritic cells, thymocytes, and activated macrophages. Here, we show that TECK is a specific agonist for a human orphan receptor called GPR-9-6. We have determined the cDNA sequence of human GPR-9-6 and cloned the corresponding murine cDNA. Human and murine GPR-9-6 expression is very high in the thymus and low in lymph nodes and spleen. RT-PCR analysis of murine GPR-9-6 expression on murine FACS-sorted thymocyte subpopulations showed that this gene is expressed in both immature and mature T cells. Additions of human or murine TECK to HEK 293/human GPR-9-6 and HEK 293/murine GPR-9-6 transfectants provoked intracytoplasmic calcium mobilization. Human TECK also induced the in vitro migration of HEK 293/human GPR-9-6 cells. These results confirm that GPR-9-6 is a specific receptor for TECK. According to the established nomenclature system, we propose to rename GPR-9-6 as CC chemokine receptor 9 (CCR9).

	Introduction

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Chemokines are a family of small, structurally related proteins that attract and activate leukocytes. The positioning of two conserved cysteines in the N-terminal region of the proteins defines four chemokine subfamilies: CXC, CC, C, and CX3C (1, 2). Chemokine receptors are G protein-coupled polypeptides with seven transmembrane domains. To date, a number of human receptors specific for CXC (CXCR1–CXCR5), CC (CCR1³–CCR8), C (XCR1), or CX3C (CX3CR1) chemokines have been described (1, 2, 3, 4, 5).

Up to now, nearly 50 chemokines have been described. Trying to dissect the chemoattractant properties of so many similar proteins, a very active field of research has been, and still is, the identification of their receptor binding specificity. Indeed, binding preferences have already been established for most chemokines. Nevertheless, the receptors for some CC chemokines such as NCC-4 (6), pulmonary- and activation-regulating chemokine (7), or TECK (8) are not known yet. Similarly, some putative CC chemokine receptors like STRL33/Bonzo (9), CKRX/HCR (10), and GPR-9-6 (EMBL accession number U45982) remain orphan. We have analyzed the phylogenetic relationships between CC chemokine receptors and orphan receptors. Our data indicate the existence of a separate group the members of which are CCR6, CCR7, STRL33/Bonzo, and GPR-9-6. Besides their structural similarities, CCR6, CCR7, and STRL33/Bonzo also share an expression pattern that is mainly restricted to lymphoid organs (9, 11, 12). Data on the expression of GPR-9-6 were not available. Here we report that the CC chemokine TECK is a specific ligand for GPR-9-6. We have also cloned the mGPR-9-6 cDNA and found that it is activated by the murine version of TECK. In addition, the constitutive RNA expression of both genes in tissues, cell lines, and thymocyte subpopulations is also reported. Following current rules for chemokine receptor nomenclature, we propose to designate GPR-9-6 as CCR9.

	Materials and Methods

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Chemokines and cells

Chemokines were purchased from Peprotech, Rocky Hill, NJ, or R&D Systems, Minneapolis, MN. The HEK 293 and MOLT4 cell lines were obtained from the American Type Culture Collection, Manassas, VA. Human and mGPR-9-6 cDNAs were cloned in pCIneo (Promega, Madison, WI), and stable transfectants were obtained after G418 selection of cells transfected with the resulting plasmids by the calcium phosphate method, as described (13). Thymocytes were purified from 5–7-wk-old female BALB/c mice using a FACSort cytometer (Becton Dickinson, Mountain View, CA) as described (14). Briefly, double-positive thymocytes were sorted as CD4⁺ CD8⁺ cells. CD4⁺ single-positive thymocytes were sorted as CD4⁺ cells after depletion of CD8⁺ thymocytes. CD8⁺ single-positive thymocytes were sorted as CD8⁺ cells. Pre-T cells were sorted as CD4^-CD8^- CD25⁺ cells after depletion of CD4⁺ and CD8⁺ thymocytes. After reanalysis, the sorted cell populations had a purity of >98%. The effect of pertussis or cholera toxins on the TECK-mediated GPR-9-6 signaling was analyzed by performing the assays on cells cultured for 16 h in 0.1 µg/ml pertussis toxin or 0.4 µg/ml cholera toxin.

Sequencing of mGPR-9-6

Based on the hGPR-9-6 sequence, a pair of oligonucleotides was designed (5'-AARTTYCARACITTYATGTGYAA-3' and 5'-GTRTGIATIATIATIGTRTARCARCA-3') and assayed in PCR amplifications using 129/SvJ mouse genomic DNA as template. A DNA fragment with the expected size was produced, and the sequencing of this material showed an open reading frame with a translated sequence that was 82% identical with that of the corresponding hGPR-9-6 sequence. Then, specific oligonucleotides were designed and used for 5'- and 3'-RACE of adapted murine thymus cDNA (Marathon cDNA amplification kit, Clontech Laboratories, Palo Alto, CA). DNA fragments corresponding to both the 5' and 3' mGPR-9-6 ends were obtained and sequenced. Finally, a DNA fragment containing the complete mGPR-9-6 coding sequence was synthesized by PCR from murine thymus cDNA.

Analysis of gene expression

Multiple tissue Northern blots (Clontech) were probed with a ³²P-labeled 1120-bp DNA fragment containing most of the hGPR-9-6 coding sequence, as recommended by the supplier. Total RNA samples from mouse tissues or FACS-sorted cell subsets were extracted with Tri-reagent (Sigma Chemical, St. Louis, MO). RNA from tissues was electrophoresed on a denaturing formaldehyde-agarose gel and blotted onto nylon Hybond membranes. Prehybridization of the membranes and hybridization with a ³²P-labeled DNA fragment containing the coding sequence of mGPR-9-6 were conducted in Rapid Hyb buffer (Amersham, Arlington Heights, IL) as recommended by the supplier. For RT-PCR analysis, total RNA from FACS-sorted cell subpopulations was reverse-transcribed as described (14). Equal amounts of cDNA were subjected to PCR amplification of mGPR-9-6 using specific forward (5'-ACGTGCTAGCCGCCATGATGCCCACAGAACTC-3') and reverse (5'-TGACCTTCAGGATCAAGACAGC-3') primers under the following conditions: 15 s at 94°C; 15 s at 59°C; 45 s at 72°C.

Calcium mobilization and chemotaxis studies

Calcium fluorometry on HEK 293 transfectant cells was conducted with indo-1-AM (Molecular Probes, Leiden, The Netherlands)-loaded cells as described (15). Each measure was done on 1-ml aliquots containing 3 x 10⁶ cells. Additions of chemokines were done in 10 µl. Cell migration assays with stable HEK 293/hGPR-9-6 or HEK 293/pCIneo transfectants were performed in a 48-well microchamber (Neuro Probe, Cabin John, MD), as described (15).

	Results and Discussion

Top Abstract Introduction Materials and Methods Results and Discussion References

 
Analysis of the phylogenetic relationships between CC chemokine receptors and orphan chemokine receptors indicates the existence of two major branches of receptors. One of them is formed by CCR6, CCR7, and the orphan receptors STRL33/Bonzo and GPR-9-6 (Fig. 1A). CCR6, CCR7, and STRL33/Bonzo also shared a restricted expression pattern, mainly limited to lymphoid organs. Moreover, unlike most CC receptors, CCR6 and CCR7 genes have coding sequences interrupted by introns (12, 16), and their ligands, liver- and activation-regulated chemokine/macrophage-inflammatory protein-3 and secondary lymphoid-tissue chemokine, respectively, are also sequence related (14). These facts prompted us to characterize in detail GPR-9-6, the other member of this group of receptors for which the only information available was the genomic sequence deposited in data banks.

View larger version (50K): [in this window] [in a new window]   FIGURE 1. Amino acid sequence similarities among chemokine receptors. A, Phylogenetic relationships among CC chemokine receptors and some orphan putative CC chemokine receptors. The tree was generated with the NJ plot program from a Clustal X multialignment. The percentage of divergence is indicated by a bar. B, Exon/intron structure of the hGPR-9-6 gene. The figure is not drawn to scale. The size of exon 2 is 48 bp. The size of introns is as indicated. Shaded areas correspond to coding sequences. C, Alignment of the predicted amino acid sequences of hGPR-9-6 and mGPR-9-6. TM, transmembrane domains. Asterisks mark sites of potential N-glycosylation. Gray boxes mark identical residues.

We followed a 5'-RACE procedure on a human thymus gt11 cDNA library and found that the protein encoded by the GPR-9-6 mRNA was 12 amino acids longer than that encoded by the genomic coding sequence previously reported. This indicates that an intron interrupts the N-terminal coding sequence, as in CCR6 and CCR7. Recently, the sequence of the region encompassing hGPR-9-6 gene has been reported (EMBL accession number AC005669). Comparison of this sequence with that of the hGPR-9-6 mRNA we report here revealed the presence of at least three exons in the hGPR-9-6 gene (Fig. 1B).

A degenerate PCR procedure with oligonucleotides based on the human sequence, combined with 5'- and 3'-RACE allowed us to clone the murine homologue of GPR-9-6 from mouse thymus cDNA. Sequencing of the PCR products obtained detected an open reading frame the predicted amino acid sequence of which was 86% identical with that of hGPR-9-6. Particularly, the 78 C-terminal residues are the same in both species; this identity is unique in the chemokine receptor family. Fig. 1C shows the alignment of the predicted 369 amino acid sequences of both hGPR-9-6 and mGPR-9-6 proteins. N32 is a potential site for N-glycosylation in both polypeptides; N388 is an additional potential site present only in the murine protein.

Analysis of hGPR-9-6 and mGPR-9-6 expression

Tissue distribution of hGPR-9-6 and mGPR-9-6 was studied by Northern blot analysis of human poly(A)⁺ RNA or mouse total RNA samples (Fig. 2). Both genes showed a high expression level in thymus; weak mRNA expression in spleen and lymph nodes was also detected. Transcript sizes were 2.7 kb for hGPR-9-6 and 3.3 kb for mGPR-9-6. Among several cell lines tested only MOLT4 showed expression of hGPR-9-6 (Fig. 2A). Because thymus was the tissue showing maximal expression of mGPR-9-6, an RT-PCR approach was used to analyze the expression of this gene in FACS-sorted thymocyte subpopulations. Murine GPR-9-6 expression was found in CD25⁺CD4^-CD8^- pre-T cells, CD4⁺CD8⁺ immature thymocytes, as well as in single positive CD4⁺ and CD8⁺ T cells (Fig. 2C).

View larger version (48K): [in this window] [in a new window]   FIGURE 2. RNA expression analysis of hGPR-9-6 and mGPR-9-6. A, Northern blots with poly(A)+ RNA from the indicated human tissues and cell lines were hybridized with a specific hGPR-9-6 probe. B, Northern blots with samples of total RNA from different mouse tissues were hybridized with a specific mGPR-9-6 probe. Sk muscle, skeletal muscle; s intestine, small intestine; ES, 129/SvJ embryonic stem cells; E9.5, E10.5, E11.5, E12.5, and E13.5, whole mouse embryos from the indicated days of gestation. C, RT-PCR analysis of mGPR-9-6 expression in thymocyte subpopulations. Total RNA samples were obtained from the indicated FACS-sorted cell subsets, reverse transcribed and PCR amplified with mGPR-9-6 specific primers. As control, amplifications of ß-actin were performed in every sample.

The ligand specificity of hGPR-9-6 was investigated by monitoring changes in the intracellular calcium concentration of HEK 293/hGPR-9-6 stable transfected cells (293/hGPR-9-6), after sequential addition of samples of chemokines. Among 36 recombinant human chemokines tested (Fig. 3A), only TECK elicited a response. The addition of 200 nM hTECK to 293/hGPR-9-6 cells resulted in significant calcium flux (Fig. 3B, upper panel), and the cell response was correlated to the chemokine dose down to 20 nM. HEK 293/mGPR-9-6 transfectant cells were also stimulated to mobilize intracellular calcium by mTECK (Fig. 3B, middle panel). Addition of a high concentration of hTECK to 293/hGPR-9-6 cells resulted in complete desensitization to a second addition of the same stimulus (Fig. 3C, upper tracing). Both human and mouse TECK were able to stimulate the human receptor in the transfectant cells, and this resulted in desensitization to a subsequent stimulus with hTECK (Fig. 3C, lower tracing). This interspecies cross-reactivity is consistent with the report by Vicari et al. (8) on mTECK-induced migration of human THP-1 cells and with the high degree of homology between the amino acid sequences of both receptors.

View larger version (48K): [in this window] [in a new window]   FIGURE 3. TECK-induced calcium mobilization and migration mediated by GPR-9-6 on HEK 293 stable transfectant cells. A, Human chemokines tested for calcium mobilization on indo-1-AM-loaded 293/hGPR-9-6 cells. SDF-1 was assayed on a host that does not express CXCR4. B, Dose-response of 293/hGPR-9-6 cells to hTECK (upper panel); 293/mGPR-9-6 cells were stimulated with 200 nM mTECK (middle panel); control pCIneo-transfected HEK 293 cells were stimulated with 200 nM hTECK or mTECK, as indicated (lower panel). C, 293/hGPR-9-6 cells were sequentially stimulated with 200 nM hTECK (upper tracing) or 200 nM mTECK (lower tracing) followed by the same concentration of hTECK. D, 293/hGPR-9-6 cells preincubated with or without pertussis toxin (PTX) were sequentially stimulated with 60 nM hTECK and 10 nM SDF-1. Arrows indicate the time of the additions. E, hTECK-induced in vitro migration of 293/hGPR-9-6 transfectant cells. Mean values from quadruplicate measures are presented; bars, SD. MDC, macrophage-derived chemoattractant; I-TAC, interferon-inducible T cell chemoattractant; LEC, liver-expressed chemokine; LARC, liver- and activation-regulated chemokine; TARC, thymus- and activation-regulated chemokine; PARC, pulmonary- and activation-regulated chemokine; BCA-1, B cell-attracting chemokine.

i

hTECK-induced calcium mobilization in MOLT4 cells

Northern analysis revealed that the MOLT4 cell line expresses hGPR-9-6 RNA. This is consistent with the thymic origin of these CD4⁺ lymphoblastic T cells. Indo-1-AM-loaded MOLT4 cells showed a high increase of intracellular calcium after stimulation with 200 nM hTECK (Fig. 4A). The cell response was correlated to the chemokine dose. MOLT4 cells were slightly more sensitive than the transfectants to low doses of the chemokine, given that 6 nM hTECK induced a detectable response. Pertussis toxin reduced but did not abolish the MOLT4 response to hTECK (Fig. 4B), while cholera toxin did not affect that response (not shown). These results are essentially identical with those obtained with the 293/hGPR-9-6 transfectants and suggest that hTECK-induced stimulation of MOLT4 cells is mediated, mainly if not exclusively, by hGPR-9-6.

View larger version (25K): [in this window] [in a new window]   FIGURE 4. hTECK-induced calcium mobilization on indo-1-AM-loaded MOLT4 cells. A, Dose response of MOLT4 cells to hTECK. B, MOLT4 cells preincubated with or without pertussis toxin (PTX) were sequentially stimulated with 60 nM hTECK followed by 100 nM SDF-1. Arrows indicate the time of the additions.

The fact that both immature and mature thymocytes express mCCR9 suggests that this receptor might play a role during the whole process of thymocyte development. Because thymic dendritic cells are producers of TECK (8), the TECK-mediated chemoattraction might be a mechanism contributing to thymocyte confinement in the thymus until completion of their development. The identification of CCR9 as the functional receptor for TECK will help to unravel the important role these proteins seem to play in thymus.

	Acknowledgments

 
We thank C. Martínez-A. for comments and support, P. Martín and M. Navarrete for excellent technical assistance, J. Satrústegui and F. Gavilanes for their assistance in the fluorometric assays, and P. Murphy and C. Gerard for their advice on chemokine receptor nomenclature.

	Footnotes

 
¹ The Departamento de Inmunología y Oncología was founded and is supported by the Consejo Superior de Investigaciones Científicas (CSIC) and Pharmacia & Upjohn. The nucleotide sequences of the genes reported in this paper have been deposited in the EMBL database with accession numbers AJ132336 (mCCR9) and AJ132337 (hCCR9). This work was supported in part by a grant from the DGICYT (PB95-0376), Ministerio de Educación y Ciencia, Spain, to C.A.

² Address correspondence and reprint requests to Dr. Gabriel Márquez, Departamento de Inmunología y Oncología Centro Nacional de Biotecnología, Universidad Autónoma de Madrid, Cantoblanco, 28049-Madrid, Spain. E-mail address:

³ Abbreviations used in this paper: CCR, CC chemokine receptor; TECK, thymus-expressed chemokine; GPR, G-protein-coupled receptor; m, murine; h, human; SDF-1, stromal cell-derived factor-1; RACE, rapid amplification of cDNA end.

Received for publication February 1, 1999. Accepted for publication March 16, 1999.

	References

Top Abstract Introduction Materials and Methods Results and Discussion References

 

1. Rollins, B. J.. 1997. Chemokines. Blood 90:909.[Free Full Text]
2. Luster, A. D.. 1998. Chemokines: chemotactic cytokines that mediate inflammation. N. Engl. J. Med. 338:436.[Free Full Text]
3. Gunn, M. D., V. N. Ngo, K. M. Ansel, E. H. Ekland, J. G. Cyster, L. T. Williams. 1998. A B-cell-homing chemokine made in lymphoid follicles activates Burkitt’s lymphoma receptor-1. Nature 391:799.[Medline]
4. Legler, D. F., M. Loetscher, R. S. Roos, L. I. Clark, M. Baggiolini, B. Moser. 1998. B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5. J. Exp. Med. 187:655.[Abstract/Free Full Text]
5. Yoshida, T., T. Imai, M. Kakizaki, M. Nishimura, S. Takagi, O. Yoshie. 1998. Identification of single C motif-1/lymphotactin receptor XCR1. J. Biol. Chem. 273:16551.[Abstract/Free Full Text]
6. Naruse, K., M. Ueno, T. Satoh, H. Nomiyama, H. Tei, M. Takeda, D. H. Ledbetter, E. V. Coillie, G. Opdenakker, N. Gunge, Y. Sakaki, M. Iio, R. Miura. 1996. A YAC contig of the human CC chemokine genes clustered on chromosome 17q11.2. Genomics 34:236.[Medline]
7. Hieshima, K., T. Imai, M. Baba, K. Shoudai, K. Ishizuka, T. Nakagawa, J. Tsuruta, M. Takeya, Y. Sakaki, K. Takatsuki, R. Miura, G. Opdenakker, J. Van Damme, O. Yoshie, H. Nomiyama. 1997. A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1 /LD78 and chemotactic for T lymphocytes, but not for monocytes. J. Immunol. 159:1140.[Abstract]
8. Vicari, A. P., D. J. Figueroa, J. A. Hedrick, J. S. Foster, K. P. Singh, S. Menon, N. G. Copeland, D. J. Gilbert, N. A. Jenkins, K. B. Bacon, A. Zlotnik. 1997. TECK: a novel CC chemokine specifically expressed by thymic dendritic cells and potentially involved in T cell development. Immunity 7:291.[Medline]
9. Liao, F., G. Alkhatib, K. W. Peden, G. Sharma, E. A. Berger, J. M. Farber. 1997. STRL33, A novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1. J. Exp. Med. 185:2015.[Abstract/Free Full Text]
10. Fan, P., H. Kyaw, K. Su, Z. Zeng, M. Augustus, K. C. Carter, Y. Li. 1998. Cloning and characterization of a novel human chemokine receptor. Biochem. Biophys. Res. Commun. 243:264.[Medline]
11. Zaballos, A., R. Varona, J. Gutierrez, P. Lind, G. Marquez. 1996. Molecular cloning and RNA expression of two new human chemokine receptor-like genes. Biochem. Biophys. Res. Commun. 227:846.[Medline]
12. Schweickart, V. L., C. J. Raport, R. Godiska, M. G. Byers, R. J. Eddy, T. B. Shows, P. W. Gray. 1994. Cloning of human and mouse EBI1, a lymphoid-specific G-protein-coupled receptor encoded on human chromosome 17q12–q21.2. Genomics 23:643.[Medline]
13. Ausubel, F. M., R. Brent, R. E. Kingston, D. D. Moore, J. G. Seidman, J. A. Smith, K. Struhl. 1989. Current Protocols in Molecular Biology Green Publishing Associates, New York.
14. Varona, R., A. Zaballos, J. Gutierrez, P. Martin, F. Roncal, J. P. Albar, C. Ardavin, G. Marquez. 1998. Molecular cloning, functional characterization and mRNA expression analysis of the murine chemokine receptor CCR6 and its specific ligand MIP-3. FEBS Lett. 440:188.[Medline]
15. Goya, I., J. Gutierrez, R. Varona, L. Kremer, A. Zaballos, G. Marquez. 1998. Identification of CCR8 as the specific receptor for the human ß-chemokine I-309: cloning and molecular characterization of murine CCR8 as the receptor for TCA-3. J. Immunol. 160:1975.[Abstract/Free Full Text]
16. Baba, M., T. Imai, M. Nishimura, M. Kakizaki, S. Takagi, K. Hieshima, H. Nomiyama, O. Yoshie. 1997. Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC chemokine LARC. J. Biol. Chem. 272:14893.[Abstract/Free Full Text]
17. Myers, S. J., L. M. Wong, I. F. Charo. 1995. Signal transduction and ligand specificity of the human monocyte chemoattractant protein-1 receptor in transfected embryonic kidney cells. J. Biol. Chem. 270:5786.[Abstract/Free Full Text]
18. Arai, H., I. F. Charo. 1996. Differential regulation of G-protein-mediated signaling by chemokine receptors. J. Biol. Chem. 271:21814.[Abstract/Free Full Text]
19. Liao, F., R. Alderson, J. Su, S. J. Ullrich, B. L. Kreider, J. M. Farber. 1997. STRL22 is a receptor for the CC chemokine MIP-3. Biochem. Biophys. Res. Commun. 236:212.[Medline]
20. Nibbs, R. J., S. M. Wylie, J. Yang, N. R. Landau, G. J. Graham. 1997. Cloning and characterization of a novel promiscuous human ß- chemokine receptor D6. J. Biol. Chem. 272:32078.[Abstract/Free Full Text]
21. Bonini, J. A., S. K. Martin, F. Dralyuk, M. W. Roe, L. H. Philipson, D. F. Steiner. 1997. Cloning, expression, and chromosomal mapping of a novel human CC-chemokine receptor (CCR10) that displays high-affinity binding for MCP-1 and MCP-3. DNA Cell Biol. 16:1249.[Medline]

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				L. Carramolino, A. Zaballos, L. Kremer, R. Villares, P. Martin, C. Ardavin, C. Martinez-A, and G. Marquez Expression of CCR9 {beta}-chemokine receptor is modulated in thymocyte differentiation and is selectively maintained in CD8+ T cells from secondary lymphoid organs Blood, February 15, 2001; 97(4): 850 - 857. [Abstract] [Full Text] [PDF]

				P. Romagnani, F. Annunziato, E. Lazzeri, L. Cosmi, C. Beltrame, L. Lasagni, G. Galli, M. Francalanci, R. Manetti, F. Marra, et al. Interferon-inducible protein 10, monokine induced by interferon gamma, and interferon-inducible T-cell alpha chemoattractant are produced by thymic epithelial cells and attract T-cell receptor (TCR) {alpha}{beta}+CD8+ single-positive T cells, TCR{gamma}{delta}+ T cells, and natural killer-type cells in human thymus Blood, February 1, 2001; 97(3): 601 - 607. [Abstract] [Full Text] [PDF]

				K. A. Papadakis, J. Prehn, V. Nelson, L. Cheng, S. W. Binder, P. D. Ponath, D. P. Andrew, and S. R. Targan The Role of Thymus-Expressed Chemokine and Its Receptor CCR9 on Lymphocytes in the Regional Specialization of the Mucosal Immune System J. Immunol., November 1, 2000; 165(9): 5069 - 5076. [Abstract] [Full Text] [PDF]

				R. Krzysiek, E. A. Lefevre, J. Bernard, A. Foussat, P. Galanaud, F. Louache, and Y. Richard Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3alpha /CCL20 in human B cells Blood, October 1, 2000; 96(7): 2338 - 2345. [Abstract] [Full Text] [PDF]

				D. Yang, Q. Chen, S. Stoll, X. Chen, O. M. Z. Howard, and J. J. Oppenheim Differential Regulation of Responsiveness to fMLP and C5a Upon Dendritic Cell Maturation: Correlation with Receptor Expression J. Immunol., September 1, 2000; 165(5): 2694 - 2702. [Abstract] [Full Text] [PDF]

				O. M. Z. Howard, H. F. Dong, A.-K. Shirakawa, and J. J. Oppenheim LEC induces chemotaxis and adhesion by interacting with CCR1 and CCR8 Blood, August 1, 2000; 96(3): 840 - 845. [Abstract] [Full Text] [PDF]

				F. Annunziato, P. Romagnani, L. Cosmi, C. Beltrame, B. H. Steiner, E. Lazzeri, C. J. Raport, G. Galli, R. Manetti, C. Mavilia, et al. Macrophage-Derived Chemokine and EBI1-Ligand Chemokine Attract Human Thymocytes in Different Stage of Development and Are Produced by Distinct Subsets of Medullary Epithelial Cells: Possible Implications for Negative Selection J. Immunol., July 1, 2000; 165(1): 238 - 246. [Abstract] [Full Text] [PDF]

				C. Murdoch and A. Finn Chemokine receptors and their role in inflammation and infectious diseases Blood, May 15, 2000; 95(10): 3032 - 3043. [Abstract] [Full Text] [PDF]

				R. M. Scoggins, J. R. Taylor Jr., J. Patrie, A. B. van't Wout, H. Schuitemaker, and D. Camerini Pathogenesis of Primary R5 Human Immunodeficiency Virus Type 1 Clones in SCID-hu Mice J. Virol., April 1, 2000; 74(7): 3205 - 3216. [Abstract] [Full Text]

				D. I. Jarmin, M. Rits, D. Bota, N. P. Gerard, G. J. Graham, I. Clark-Lewis, and C. Gerard Cutting Edge: Identification of the Orphan Receptor G-Protein-Coupled Receptor 2 as CCR10, a Specific Receptor for the Chemokine ESkine J. Immunol., April 1, 2000; 164(7): 3460 - 3464. [Abstract] [Full Text] [PDF]

				J. Gosling, D. J. Dairaghi, Y. Wang, M. Hanley, D. Talbot, Z. Miao, and T. J. Schall Cutting Edge: Identification of a Novel Chemokine Receptor That Binds Dendritic Cell- and T Cell-Active Chemokines Including ELC, SLC, and TECK J. Immunol., March 15, 2000; 164(6): 2851 - 2856. [Abstract] [Full Text] [PDF]

				P. M. Murphy, M. Baggiolini, I. F. Charo, C. A. Hebert, R. Horuk, K. Matsushima, L. H. Miller, J. J. Oppenheim, and C. A. Power International Union of Pharmacology. XXII. Nomenclature for Chemokine Receptors Pharmacol. Rev., March 1, 2000; 52(1): 145 - 176. [Abstract] [Full Text] [PDF]

				C.-R. Yu, K. W. C. Peden, M. B. Zaitseva, H. Golding, and J. M. Farber CCR9A and CCR9B: Two Receptors for the Chemokine CCL25/TECK/Ck{beta}-15 That Differ in Their Sensitivities to Ligand J. Immunol., February 1, 2000; 164(3): 1293 - 1305. [Abstract] [Full Text] [PDF]

				A. M. Norment, L. Y. Bogatzki, B. N. Gantner, and M. J. Bevan Murine CCR9, a Chemokine Receptor for Thymus-Expressed Chemokine That Is Up-Regulated Following Pre-TCR Signaling J. Immunol., January 15, 2000; 164(2): 639 - 648. [Abstract] [Full Text] [PDF]

				B. A. Zabel, W. W. Agace, J. J. Campbell, H. M. Heath, D. Parent, A. I. Roberts, E. C. Ebert, N. Kassam, S. Qin, M. Zovko, et al. 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., November 1, 1999; 190(9): 1241 - 1256. [Abstract] [Full Text] [PDF]

				B.-S. Youn, C. H. Kim, F. O. Smith, and H. E. Broxmeyer TECK, an Efficacious Chemoattractant for Human Thymocytes, Uses GPR-9-6/CCR9 as a Specific Receptor Blood, October 1, 1999; 94(7): 2533 - 2536. [Abstract] [Full Text] [PDF]

				W. Wang, H. Soto, E. R. Oldham, M. E. Buchanan, B. Homey, D. Catron, N. Jenkins, N. G. Copeland, D. J. Gilbert, N. Nguyen, et al. Identification of a Novel Chemokine (CCL28), which Binds CCR10 (GPR2) J. Biol. Chem., July 14, 2000; 275(29): 22313 - 22323. [Abstract] [Full Text] [PDF]

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