Expression cloning of cell surface receptors for the CpG oligodeoxynucleotide/CXCL14 complex

CpG oligodeoxynucleotides (ODNs) induce innate immune responses in dendritic cells and macrophages. A few CpG ODN receptor molecules have been reported. However, recent studies revealed that CXCL14 is required for the function of CpG ODNs in vivo, thereby increasing the importance of cell surface receptors for the CpG ODN/CXCL14 complex. To identify such CpG ODN/CXCL14 receptor molecules, we performed expression cloning using cDNA libraries of mouse dendritic cells and macrophage-derived cells. Consequently, we successfully isolated cDNAs encoding glycoprotein nonmetastatic melanoma protein B (Gpnmb), scavenger receptor class B1 (Scarb1), and immunoglobulin superfamily 8 (Igsf8). Subsequent experiments revealed that Gpnmb only bound to CpG ODNs, while Igsf8, Scarb1, and Cd36 interacted with both CpG ODNs and the CpG ODN/CXCL14 complex. Igsf3 and Rage only bound to the Cy3-ODN2395/CXCL14 complex. These results suggest that intracellular uptake of the CpG ODN/CXCL14 complex is mediated by multiple types of cell surface receptors.