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. 1999 Nov 1;190(9):1241-56. doi: 10.1084/jem.190.9.1241.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Calcium
  • Cell Line
  • Chemokines, CC / genetics
  • Chemokines, CC / 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
  • Receptors, Chemokine / immunology*
  • Receptors, Lymphocyte Homing / immunology
  • T-Lymphocytes / metabolism*
  • Thymus Gland / immunology*
  • Transfection

Substances

  • Antibodies, Monoclonal
  • CC chemokine receptor 9
  • CCL25 protein, human
  • Chemokines, CC
  • RNA, Messenger
  • Receptors, CCR
  • Receptors, Chemokine
  • Receptors, Lymphocyte Homing
  • Calcium