Cloning and Characterization of a Specific Receptor for the Novel CC Chemokine MIP-3α from Lung Dendritic Cells

Abstract

Dendritic cells are potent antigen-presenting cells involved in the initiation of immune responses. The trafficking of these cells to tissues and lymph nodes is mediated by members of the chemokine family. Recently, a novel CC chemokine known as MIP-3α or liver and activation-regulated chemokine has been identified from the EMBL/GenBank/DDBJ expressed sequence tag database. In the present study, we have shown that the messenger RNA for MIP-3α is expressed predominantly in inflamed and mucosal tissues. MIP-3α produced either synthetically or by human embryonic kidney 293 cells is chemotactic for CD34+-derived dendritic cells and T cells, but is inactive on monocytes and neutrophils. MIP-3α was unable to displace the binding of specific CC or CXC chemokines to stable cell lines expressing their respective high affinity receptors, namely CCR1–5 and CXCR1 and CXCR2, suggesting that MIP-3α acts through a novel CC chemokine receptor. Therefore, we used degenerate oligonucleotide-based reverse transcriptase PCR to identify candidate MIP-3α receptors in lung dendritic cells. Our results show that the orphan receptor known as GCY-4, CKRL-3, or STRL-22 is a specific receptor for MIP-3α, and that its activation leads to pertussis toxin–sensitive and phospholipase C–dependent intracellular Ca2+ mobilization when it is expressed in HEK 293 cells.

IL-1β and IFN-γ induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice

“…MIP-3α might contribute to the attraction of memory T-cells to the grafts [20,21]. Expression of IL-15 in the graft and kidney tissue was constitutive, with no major changes in expression after 8 h or 6 days.…”

“…Moreover, high serum levels of IP-10 are seen in Type 1 diabetic patients [18]. MIP-3α is a CC chemokine which attracts memory T-lymphocytes and dendritic cells expressing the CCR6 receptor [19,20,21]. The expression of MIP-3α is up-regulated in psoriatic skin [22], atopic dermatitis [23] and rheumatoid arthritis [24] and MIP-3α is involved in the amplification of local inflammatory responses in the liver [25].…”

Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gp100

“…Many studies showed that DC could attract T cells by secreting chemokines. 38,39 Our previous study demonstrated that Lptn-DC exhibited enhanced preferential chemotaxis to T cells, and were capable of delivering tumor antigen peptide more efficiently to induce tumor rejection in 3LL Lewis lung carcinoma models. 22,40 Certain human cancers have been found to express TAAs that can be recognized immunologically, such as melanoma antigens, polymorphic epithelial mucin (PEM), HER2/neu protooncogen and so on.…”

The chemokine system: tuning and shaping by regulation of receptor expression and coupling in polarized responses

“…However, most chemokine receptors of plasmacytoid DC, in particular those for inflammatory chemokines, are apparently not functional in circulating cells (37). Langerhans cells purified from skin or generated in vitro from CD34 + precursors are characterized by the expression of CCR6, the receptor for CCL20/MIP-3a in addition to the receptors expressed by mono-DC (38). CCR6 interacts also with defensins that have agonist activity for DC (39).…”