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PMID: 10544196 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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.

The Journal of experimental medicine ·Vol. 190 ·No. 9 ·1999-11-01 ·Pages 1241-56

Zabel BA, Agace WW, Campbell JJ, Heath HM, Parent D, Roberts AI, Ebert EC, Kassam N, Qin S, Zovko M, LaRosa GJ, Yang LL, Soler D, Butcher EC, Ponath PD, Parker CM, Andrew DP

Abstract

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.

MeSH Terms
Antibodies, Monoclonal CD4-Positive T-Lymphocytes/metabolism CD8-Positive T-Lymphocytes/metabolism Calcium Cell Line Chemokines, CC/genetics,pharmacology Chemotaxis/immunology Flow Cytometry Gene Expression Regulation/immunology Humans Intestinal Mucosa/immunology Lymphocyte Activation/immunology Lymphocyte Subsets/immunology RNA, Messenger/immunology Receptors, CCR Receptors, Chemokine/genetics,immunology Receptors, Lymphocyte Homing/immunology T-Lymphocytes/metabolism Thymus Gland/immunology Transfection
Chemicals
Antibodies, Monoclonal CC chemokine receptor 9 CCL25 protein, human Chemokines, CC RNA, Messenger Receptors, CCR Receptors, Chemokine Receptors, Lymphocyte Homing Calcium
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Zabel B A
LeukoSite, Inc., Cambridge, Massachusetts 02142, USA.
Agace W W
Campbell J J
Heath H M
Parent D
Roberts A I
Ebert E C
Kassam N
Qin S
Zovko M
LaRosa G J
Yang L L
Soler D
Butcher E C
Ponath P D
Parker C M
Andrew D P
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.190.9.1241
Published
1999-11-01
Pages
1241-56
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2195678
Subset
IM
Grants
NIAID NIH HHS · AI37832 · United States
NIDDK NIH HHS · DK52978 · United States
NIDDK NIH HHS · DK42166 · United States
External Links
PubMed source DOI: 10.1084/jem.190.9.1241 PMC Full Text View journal details
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