Sphingomyelin and ceramide are physiological ligands for human LMIR3/CD300f, inhibiting FcεRI-mediated mast cell activation

Izawa, Kumi; Isobe, Masamichi; Matsukawa, Toshihiro; S, Itó; Maehara, Akie; Takahashi, Mariko; Yamanishi, Yoshihiro; Kaitani, Ayako; Oki, Toshihiko; Okumura, Ko; Kitamura, Toshio; Kitaura, Jiro

doi:10.1016/j.jaci.2013.08.008

Cited by 45 publications

(67 citation statements)

References 14 publications

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“…CD300lf is an inhibitory receptor, and their paired activating receptor is CD300ld. CD300lf is associated with the suppression of an allergic reaction with ceramide as a ligand (18). To determine if KO of CD300lf alone was linked to the loss of the MNV-induced CPE, we created CD300lf KO cells by introducing the gRNA targeting CD300lf into RAW/Cas9 cells (CD300lf KO cells).…”

Section: Resultsmentioning

confidence: 99%

Functional receptor molecules CD300lf and CD300ld within the CD300 family enable murine noroviruses to infect cells

Haga

Fujimoto

Takai‐Todaka

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

160

154

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Norovirus is the leading cause of acute gastroenteritis worldwide. Since the discovery of human norovirus (HuNoV), an efficient and reproducible norovirus replication system has not been established in cultured cells. Although limited amounts of virus particles can be produced when the HuNoV genome is directly transfected into cells, the HuNoV cycle of infection has not been successfully reproduced in any currently available cell-culture system. Those results imply that the identification of a functional cell-surface receptor for norovirus might be the key to establishing a norovirus culture system. Using a genome-wide CRISPR/Cas9 guide RNA library, we identified murine CD300lf and CD300ld as functional receptors for murine norovirus (MNV). The treatment of susceptible cells with polyclonal antibody against CD300lf significantly reduced the production of viral progeny. Additionally, ectopic CD300lf expression in nonsusceptible cell lines derived from other animal species enabled MNV infection and progeny production, suggesting that CD300lf has potential for dictating MNV host tropism. Furthermore, CD300ld, which has an amino acid sequence in the N-terminal region of its extracellular domain that is highly homologous to that of CD300lf, also functions as a receptor for MNV. Our results indicate that direct interaction of MNV with two cell-surface molecules, CD300lf and CD300ld, dictates permissive noroviral infection.

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Section: Resultsmentioning

confidence: 99%

Functional receptor molecules CD300lf and CD300ld within the CD300 family enable murine noroviruses to infect cells

Haga

Fujimoto

Takai‐Todaka

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

160

154

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“…To generate the chimeric receptor hCD300e-CD3ζ, SLAM signal sequence-Flag-hCD300e, excluding transmembrane and intracellular domains, was fused to the transmembrane domain of human CD300f followed by the intracellular domain of human CD3ζ (Naoki Matsumoto, The University of Tokyo, Tokyo, Japan). mCD300e-CD3ζ or hCD300e-CD3ζ was subcloned into pMXs-IP to generate pMXs-Flag-mCD300e-CD3ζ or Flag-hCD30 0e-CD3ζ-IP (15,19,21). To generate mCD300e-N84Q mutant, two-step PCR mutagenesis was performed using pMXs-Flag-mCD300e-IP as a template.…”

Section: Gene Expression Analysismentioning

confidence: 99%

“…Multiple studies showed that lipids or lipid-binding proteins act as ligands for several members of mouse and human CD300 family (14)(15)(16)(17)(18)(19)(20). For example, the recognition of ceramide by mouse CD300f or of ceramide and sphingomyelin by human CD300f induces the suppression of various inflammatory responses (15,(21)(22)(23)(24). CD300a, CD300b, CD300c, or CD300f binds to phosphatidylserine, thereby positively or negatively regulating apoptotic cell-mediated immune responses (16,17,19,20).…”

Section: Introductionmentioning

confidence: 99%

The CD300e molecule in mice is an immune-activating receptor

Isobe

Izawa

Sugiuchi

et al. 2018

Journal of Biological Chemistry

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“…In this sense, CD300f is a promising target because blocking of CD300f function stimulates innate host responses that can overcome both primary bacterial infections and secondary cosmic infections. Because human CD300f binds both ceramide and sphingomyelin 20 , a novel drug specifically disrupting this binding may be effective against bacterial infections. In addition, it is possible that combined targeted therapies will synergistically improve the survival rates of septic patients.…”

Section: Discussionmentioning

confidence: 99%

Disrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment

Izawa

Maehara

Isobe

et al. 2017

Sci Rep

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Sepsis is a serious clinical problem. Negative regulation of innate immunity is associated with sepsis progression, but the underlying mechanisms remains unclear. Here we show that the receptor CD300f promotes disease progression in sepsis. CD300f −/− mice were protected from death after cecal ligation and puncture (CLP), a murine model of septic peritonitis. CD300f was highly expressed in mast cells and recruited neutrophils in the peritoneal cavity. Analysis of mice (e.g., mast cell-deficient mice) receiving transplants of wild-type or CD300f −/− mast cells or neutrophils indicated that CD300f deficiency did not influence intrinsic migratory abilities of neutrophils, but enhanced neutrophil chemoattractant production (from mast cells and neutrophils) in the peritoneal cavity of CLP-operated mice, leading to robust accumulation of neutrophils which efficiently eliminated Escherichia coli. Ceramide-CD300f interaction suppressed the release of neutrophil chemoattractants from Escherichia coli-stimulated mast cells and neutrophils. Administration of the reagents that disrupted the ceramide-CD300f interaction prevented CLP-induced sepsis by stimulating neutrophil recruitment, whereas that of ceramide-containing vesicles aggravated sepsis. Extracellular concentrations of ceramides increased in the peritoneal cavity after CLP, suggesting a possible role of extracellular ceramides, CD300f ligands, in the negative-feedback suppression of innate immune responses. Thus, CD300f is an attractive target for the treatment of sepsis.

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Sphingomyelin and ceramide are physiological ligands for human LMIR3/CD300f, inhibiting FcεRI-mediated mast cell activation

Cited by 45 publications

References 14 publications

Functional receptor molecules CD300lf and CD300ld within the CD300 family enable murine noroviruses to infect cells

Functional receptor molecules CD300lf and CD300ld within the CD300 family enable murine noroviruses to infect cells

The CD300e molecule in mice is an immune-activating receptor

Disrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment

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