Cutting Edge: SR-PSOX/CXC Chemokine Ligand 16 Mediates Bacterial Phagocytosis by APCs Through its Chemokine Domain

Shimaoka, Takeshi; Nakayama, Takashi; Kume, Noriaki; Takahashi, Shuntaro; Yamaguchi, Junko; Minami, Manabu; Hayashida, Kazutaka; Kita, Toru; Ohsumi, Jun; Yoshie, Osamu; Yonehara, Shin

doi:10.4049/jimmunol.171.4.1647

Cited by 144 publications

(144 citation statements)

References 21 publications

Supporting

Mentioning

142

Contrasting

Order By: Relevance

“…Firststrand complementary DNA (cDNA) was synthesized using oligo(dT) [12][13][14][15][16][17][18] primers (Amersham Pharmacia Biotech, Piscat-away, NJ) and SuperScript II reverse transcriptase (Invitrogen). The amount of cDNA for amplification was adjusted to the amount of RNA measured by optical density meter as well as ␤-actin polymerase chain reaction (PCR) products, using serially diluted cDNA.…”

Section: Methodsmentioning

confidence: 99%

Pathogenic role of the CXCL16–CXCR6 pathway in rheumatoid arthritis

Nanki¹,

Shimaoka²,

Hayashida³

et al. 2005

Arthritis & Rheumatism

Self Cite

135

114

View full text Add to dashboard Cite

Objective. Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with massive T cell infiltration into the synovium. The accumulated T cells express type 1 cytokines, such as interferon-␥ (IFN␥) and tumor necrosis factor ␣, and activated markers of inflammation, such as CD154 and inducible costimulator (ICOS). It is thought that chemokines contribute to T cell accumulation in the synovium. In this study, we examined the role of CXCL16 and CXCR6 in T cell migration and stimulation in RA synovium.Methods. Expression of CXCL16 and CXCR6 was analyzed by immunohistochemistry, reverse transcription-polymerase chain reaction, Western blotting, and/or flow cytometry. Migration activity was assessed using a chemotaxis chamber. IFN␥ production was analyzed by enzyme-linked immunosorbent assay. The effect of anti-CXCL16 monoclonal antibody on murine collagen-induced arthritis (CIA) was evaluated.Results. CXCL16 was expressed in RA synovium.

show abstract

Section: Methodsmentioning

confidence: 99%

Pathogenic role of the CXCL16–CXCR6 pathway in rheumatoid arthritis

Nanki¹,

Shimaoka²,

Hayashida³

et al. 2005

Arthritis & Rheumatism

Self Cite

135

114

View full text Add to dashboard Cite

show abstract

“…Membrane-bound, it serves as a scavenger receptor for phosphatidylserine and oxidised low-density lipoprotein [6], and facilitates the phagocytosis of bacteria [7]. Immunohistochemical analysis suggests that CXCL16 is expressed by lipid-laden macrophages in the intima of atherosclerotic plaques and by valvular and neocapillary endothelial cells in patients with infective endocarditis, suggesting a role in the pathogenesis of both diseases [8,9].…”

Section: Introductionmentioning

confidence: 99%

Site‐directed mutagenesis of the chemokine receptor CXCR6 suggests a novel paradigm for interactions with the ligand CXCL16

2008

View full text Add to dashboard Cite

Chemokine receptor CXCR6 mediates the chemotaxis and adhesion of leukocytes to soluble and membrane-anchored forms of CXCL16, and is an HIV-1 co-receptor. Here, we describe the effects of mutation of acidic extracellular CXCR6 residues on receptor function. Although most CXCR6 mutants examined were expressed at levels similar to wild-type (WT) CXCR6, an N-terminal E3Q mutant was poorly expressed, which may explain previously reported protective effects of a similar single nucleotide polymorphism, with respect to late-stage HIV-1 infection. In contrast to several other chemokine receptors, mutation of the CXCR6 N terminus and inhibition of post-translational modifications of this region were without effect on receptor function. Likewise, N-terminal extension of CXCL16 resulted in a protein with decent potency and efficacy in chemotaxis and not, as anticipated, a CXCR6 antagonist. D176N and E274Q CXCR6 mutants were unable to interact with soluble CXCL16, suggesting a critical role for D176 and E274 in ligand binding. Intriguingly, although unable to interact with soluble CXCL16, the E274Q mutant could promote robust adhesion to membrane-anchored CXCL16, suggesting that soluble and membrane-bound forms of CXCL16 possess distinct conformations. Collectively, our data suggest a novel paradigm for the CXCR6:CXCL16 interaction, a finding which may impact the discovery of small-molecule antagonists of CXCR6.

show abstract

“…In addition to the seven differentially expressed genes within Idd4, Cxcl16 and C1qbp, which were expressed similarly in NOR and NOR.NOD-Idd4 mice, were considered good T1D susceptibility candidates because of their known involvement in immune response. CXCL16, expressed at high levels on M /DCs, induces a strong chemotactic attraction of activated CD8 cells (37) and a subset of NK-T cells (38) and mediates adhesion and phagocytosis of Gram-negative and -positive bacteria (39,40). C1QBP is a ubiquitously expressed, multiligand binding protein involved the classical complement pathway.…”

Section: Pld2mentioning

confidence: 99%

Molecular Genetic Analysis of the Idd4 Locus Implicates the IFN Response in Type 1 Diabetes Susceptibility in Nonobese Diabetic Mice

Ivakine

Gulban

Mortin-Toth

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

High-resolution mapping and identification of the genes responsible for type 1 diabetes (T1D) has proved difficult because of the multigenic etiology and low penetrance of the disease phenotype in linkage studies. Mouse congenic strains have been useful in refining Idd susceptibility loci in the NOD mouse model and providing a framework for identification of genes underlying complex autoimmune syndromes. Previously, we used NOD and a nonobese diabetes-resistant strain to map the susceptibility to T1D to the Idd4 locus on chromosome 11. Here, we report high-resolution mapping of this locus to 1.4 megabases. The NOD Idd4 locus was fully sequenced, permitting a detailed comparison with C57BL/6 and DBA/2J strains, the progenitors of T1D resistance alleles found in the nonobese diabetes-resistant strain. Gene expression arrays and quantitative real-time PCR were used to prioritize Idd4 candidate genes by comparing macrophages/dendritic cells from congenic strains where allelic variation was confined to the Idd4 interval. The differentially expressed genes either were mapped to Idd4 or were components of the IFN response pathway regulated in trans by Idd4. Reflecting central roles of Idd4 genes in Ag presentation, arachidonic acid metabolism and inflammation, phagocytosis, and lymphocyte trafficking, our combined analyses identified Alox15, Alox12e, Psmb6, Pld2, and Cxcl16 as excellent candidate genes for the effects of the Idd4 locus.

show abstract

Cutting Edge: SR-PSOX/CXC Chemokine Ligand 16 Mediates Bacterial Phagocytosis by APCs Through its Chemokine Domain

Cited by 144 publications

References 21 publications

Pathogenic role of the CXCL16–CXCR6 pathway in rheumatoid arthritis

Pathogenic role of the CXCL16–CXCR6 pathway in rheumatoid arthritis

Site‐directed mutagenesis of the chemokine receptor CXCR6 suggests a novel paradigm for interactions with the ligand CXCL16

Molecular Genetic Analysis of the Idd4 Locus Implicates the IFN Response in Type 1 Diabetes Susceptibility in Nonobese Diabetic Mice

Contact Info

Product

Resources

About