Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes.

Abstract

SummaryA human receptor that is selective for the CXC chemokines IP10 and Mig was cloned and characterized. The receptor cDNA has an open reading frame of 1104-bp encoding a protein of 368 amino acids with a molecular mass of 40,659 dalton. The sequence includes seven putative transmembrane segments characteristic of G-protein coupled receptors. It shares 40.9 and 40.3% identical amino acids with the two IL-8 receptors, and 34.2-36.9% identity with the five known CC chemokine receptors. The IPl0/Mig receptor is highly expressed in IL-2-activated T lymphocytes, but is not detectable in resting T lymphocytes, B lymphocytes, monocytes and granulocytes. It mediates Ca 2+ mobilization and chernotaxis in response to IP10 and Mig, but does not recognize the CXC-chemokines IL-8, GROom, NAP-2, GCP-2, ENA78, PF4, the CC-chemokines MCP-1, MCP-2, MCP-3, MCP-4, MIP-lot, MIP-I[~, RANTES, I309, eotaxin, nor lymphotactin. The exclusive expression in activated T-lymphocytes is of high interest since the receptors for chemokines which have been shown so far to attract lymphocytes, e.g., MCP-1, MCP-2, MCP-3, MIP-lot, MIP-I[3, and R_ANTES, are also found in monocytes and granulocytes. The present observations suggest that the IP10/Mig receptor is involved in the selective recruitment of effector T cells.

Enhanced Expression of CXCL10 in Inflammatory Bowel Disease

“…CXCL10 is a ligand for the receptor CXCR3, which is also the case for CXCL9 (former MIG) and CXCL11 (former I-TAC). Binding of ligand to CXCR3 is crucial for chemotaxis of these receptor positive cells to inflammatory sites (5). CXCL10 is regarded as a chemoattractant preferentially for activated T-cells (6) and particularly Th1 cells (7).…”

Single nucleotide polymorphisms in the coding regions of human CXC-chemokine receptors CXCR1, CXCR2 and CXCR3

“…GPR9 corresponds to the putative CXCR3 exon 2 and consists of partial CXCR3 coding region [CXCR3 (5-368)] of 1095 bp and the 3′ untranslated region (3′UTR). 13 Since the optimal size of PCR product for SSCP was determined to be 200-400 bp in the previous studies, 50 specific primer sets were designed to amplify six overlapping segments of the entire coding region of CXCR1. CXCR2 was divided into five fragments and CXCR3 exon 2 into five as well.…”

“…CXCR2 was divided into five fragments and CXCR3 exon 2 into five as well. Because no flanking sequence data were available to design the primer set for exon 1, the sense primer was designed within 5′ untranslated region (5′UTR) based on the published cDNA sequence of CXCR3 (X95876) 13 and the antisense primer within intron 1 based on the results of direct sequencing (data not shown).…”

“…It is strongly expressed in IL-2-activated T lymphocytes, but not in freshly isolated peripheral blood leukocytes or related cell lines. 13 However, its intense expression was shown in T cells isolated from synovial fluid from patients with RA, from tissues of chronically inflamed vaginal and colonic mucosa, or from cerebrospinal fluid from patients with multiple sclerosis. 14,15 Activated Th1/Tc1 subsets have been shown to express CXCR3 and CCR5.…”

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“…CXCR3 (GPR9; CD183), the receptor for CXCL10 also binds the CXC chemokines CXCL9 and CXCL11 [19]. Recent studies of the CNS have suggested that CXCR3 additionally binds CCL21 [20].…”