Identification of human CCR8 as a CCL18 receptor

Islam, Saleem; Ling, Morris; Leung, John; Shreffler, Wayne G.; Luster, Andrew D.

doi:10.1084/jem.20130240

Cited by 171 publications

(174 citation statements)

References 31 publications

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“…The recent identification of CCR8 as the major receptor of CCL18 has permitted the functional evaluation of CCL18 and its murine analog CCL8. 13 In our study, immunohistochemical analysis revealed the presence of CCL18 in intrarenal cells with a mononuclear appearance. Consecutive sections identified macrophages and myeloid DCs 25 coexpressing CCL18.…”

Section: Adoptively Transferred Monocytes Restore Kidney Injury In Nesupporting

confidence: 58%

“…In 2013, Islam et al 13 reported the murine CCL8 (mCCL8) as its functional analog. Both chemokines acted through CC chemokine receptor 8 (CCR8) and were induced in alternatively activated macrophages [14][15][16][17] as well as in similar diseases.…”

mentioning

confidence: 99%

“…[18][19][20] Similar cytokine patterns regulated the induction of CCL18 and mCCL8. 13 Therefore, we aimed to investigate the functional role of CCR8 in crescentic GN by analyzing Ccr8 2/2 mice in an experimental model of murine crescentic GN.…”

mentioning

confidence: 99%

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CC Chemokine Ligand 18 in ANCA-Associated Crescentic GN

Brix¹,

Stege²,

Disteldorf³

et al. 2015

Journal of the American Society of Nephrology

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ANCA-associated vasculitis is the most frequent cause of crescentic GN. To define new molecular and/or cellular biomarkers of this disease in the kidney, we performed microarray analyses of renal biopsy samples from patients with ANCA-associated crescentic GN. Expression profiles were correlated with clinical data in a prospective study of patients with renal ANCA disease. CC chemokine ligand 18 (CCL18), acting through CC chemokine receptor 8 (CCR8) on mononuclear cells, was identified as the most upregulated chemotactic cytokine in patients with newly diagnosed ANCA-associated crescentic GN. Macrophages and myeloid dendritic cells in the kidney were detected as CCL18-producing cells. The density of CCL18 + cells correlated with crescent formation, interstitial inflammation, and impairment of renal function. CCL18 protein levels were higher in sera of patients with renal ANCA disease compared with those in sera of patients with other forms of crescentic GN. CCL18 serum levels were higher in patients who suffered from ANCA-associated renal relapses compared with those in patients who remained in remission. Using a murine model of crescentic GN, we explored the effects of the CCL18 murine functional analog CCL8 and its receptor CCR8 on kidney function and morphology. Compared with wild-type mice, Ccr8 2/2 mice had significantly less infiltration of pathogenic mononuclear phagocytes. Furthermore, Ccr8 2/2 mice maintained renal function better and had reduced renal tissue injury. In summary, our data indicate that CCL18 drives renal inflammation through CCR8-expressing cells and could serve as a biomarker for disease activity and renal relapse in ANCA-associated crescentic GN.

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Section: Adoptively Transferred Monocytes Restore Kidney Injury In Nesupporting

confidence: 58%

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confidence: 99%

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CC Chemokine Ligand 18 in ANCA-Associated Crescentic GN

Brix¹,

Stege²,

Disteldorf³

et al. 2015

Journal of the American Society of Nephrology

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“…CCR8 is a beta chemokine receptor with a known role in induction of chemotaxis in Th2 cells via its two ligands CCL1 and CCL18 [50], and functions as a co-receptor for enveloped viruses including HIV [51,52]. The CCR8 axis has been found to be activated in urothelial and renal carcinomas resulting in immune response impairment, and it is responsible for apoptosis inhibition in lymphoma [53,54].…”

Section: Resultsmentioning

confidence: 99%

Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8

Berenguer

Lagerweij

Zhao

et al. 2018

J of Extracellular Vesicle

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Cancer cells release extracellular vesicles (EVs) that contain functional biomolecules such as RNA and proteins. EVs are transferred to recipient cancer cells and can promote tumour progression and therapy resistance. Through RNAi screening, we identified a novel EV uptake mechanism involving a triple interaction between the chemokine receptor CCR8 on the cells, glycans exposed on EVs and the soluble ligand CCL18. This ligand acts as bridging molecule, connecting EVs to cancer cells. We show that glioblastoma EVs promote cell proliferation and resistance to the alkylating agent temozolomide (TMZ). Using in vitro and in vivo stem-like glioblastoma models, we demonstrate that EV-induced phenotypes are neutralised by a small molecule CCR8 inhibitor, R243. Interference with chemokine receptors may offer therapeutic opportunities against EV-mediated cross-talk in glioblastoma.

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“…With regard to fibrosis, CCL18 has been found to be elevated in EoE [47]. Studies by the Luster laboratory identified CCR8 as the CCL18 receptor, and both were found to be elevated in active EoE biopsies [48]. Together, these studies have translational implications for both anti-eosinophil strategies using biologics that provide siglec-8, IL-13, CCR8, and/or mast cell blockade.…”

Section: New Pathophysioloigic Insights Have Potential Therapeutic Valuementioning

confidence: 87%

Non-IgE Medicated Food Allergy: Eosinophilic Esophagitis Update on the Pathogenesis, Clinical Features, and Management of Eosinophilic Esophagitis in Children

Greenhawt

Aceves

2014

Curr Pediatr Rep

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Eosinophilic esophagitis (EoE) is a chronic allergic disorder of increasing worldwide prevalence. Diagnosis and management require upper gastrointestinal endoscopy with biopsy. Therapeutic strategies in children and adults include empiric and testing-based elimination diets as well as topical esophageal corticosteroids. The last 12 months have provided a number of insights including updated diagnostic/management guidelines, the role of PPI therapy, and an understanding that EoE disease mechanisms rely on basophils and mast cells in addition to eosinophils. Novel diagnostic techniques have been described and include the esophageal string test and a molecular gene array panel. In addition, new techniques for assessing esophageal rigidity have been reported. In this review, we summarize the most impactful findings in EoE over the last 12-15 months.

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Identification of human CCR8 as a CCL18 receptor

Abstract: CCL18 is an endogenous agonist of the human CCR8 receptor.

Cited by 171 publications

References 31 publications

CC Chemokine Ligand 18 in ANCA-Associated Crescentic GN

CC Chemokine Ligand 18 in ANCA-Associated Crescentic GN

Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8

Non-IgE Medicated Food Allergy: Eosinophilic Esophagitis Update on the Pathogenesis, Clinical Features, and Management of Eosinophilic Esophagitis in Children

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