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.
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 alpha4beta7(high) 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 alpha4beta7(-)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.
Zabel
B A
BA
LeukoSite, Inc., Cambridge, Massachusetts 02142, USA.
Agace
W W
WW
Campbell
J J
JJ
Heath
H M
HM
Parent
D
D
Roberts
A I
AI
Ebert
E C
EC
Kassam
N
N
Qin
S
S
Zovko
M
M
LaRosa
G J
GJ
Yang
L L
LL
Soler
D
D
Butcher
E C
EC
Ponath
P D
PD
Parker
C M
CM
Andrew
D P
DP
D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002118:Calcium; D002460:Cell Line; D019742:Chemokines, CC / Q000235:genetics / Q000494:pharmacology*; D002633:Chemotaxis / Q000276:immunology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D012333:RNA, Messenger / Q000276:immunology; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism*; D013950:Thymus Gland / Q000276:immunology*; D014162:Transfection
D000911:Antibodies, Monoclonal; C119309:CC chemokine receptor 9; C108074:CCL25 protein, human; D019742:Chemokines, CC; D012333:RNA, Messenger; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing; D002118:Calcium