Inhibitory NK Receptor Ly49Q Is Expressed on Subsets of Dendritic Cells in a Cellular Maturation- and Cytokine Stimulation-Dependent Manner

Toyama–Sorimachi, Noriko; Omatsu, Yoshiki; Onoda, Atsuko; Tsujimura, Yusuke; Iyoda, Tomonori; Kikuchi-Maki, Akiko; Sorimachi, Hiroyuki; Dohi, Taeko; Taki, Shinsuke; Inaba, Kayo; Karasuyama, Hajime

doi:10.4049/jimmunol.174.8.4621

Cited by 43 publications

(36 citation statements)

References 48 publications

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“…Ly49Q is expressed on myeloid lineage cells, in particular plasmacytoid dendritic cells (4,31). Thus, cell types other than NK cells use receptor masking to adapt receptor accessibility and consequently receptor function to self-MHC-I.…”

Section: Ly49b and Ly49qmentioning

confidence: 99%

Interactions of Ly49 Family Receptors with MHC Class I Ligands in trans and cis

Scarpellino

Oeschger

Guillaume

et al. 2007

The Journal of Immunology

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The Ly49A NK cell receptor interacts with MHC class I (MHC-I) molecules on target cells and negatively regulates NK cell-mediated target cell lysis. We have recently shown that the MHC-I ligand-binding capacity of the Ly49A NK cell receptor is controlled by the NK cells’ own MHC-I. To see whether this property was unique to Ly49A, we have investigated the binding of soluble MHC-I multimers to the Ly49 family receptors expressed in MHC-I-deficient and -sufficient C57BL/6 mice. In this study, we confirm the binding of classical MHC-I to the inhibitory Ly49A, C and I receptors, and demonstrate that detectable MHC-I binding to MHC-I-deficient NK cells is exclusively mediated by these three receptors. We did not detect significant multimer binding to stably transfected or NK cell-expressed Ly49D, E, F, G, and H receptors. Yet, we identified the more distantly related Ly49B and Ly49Q, which are not expressed by NK cells, as two novel MHC-I receptors in mice. Furthermore, we show using MHC-I-sufficient mice that the NK cells’ own MHC-I significantly masks the Ly49A and Ly49C, but not the Ly49I receptor. Nevertheless, Ly49I was partly masked on transfected tumor cells, suggesting that the structure of Ly49I is compatible in principal with cis binding of MHC-I. Finally, masking of Ly49Q by cis MHC-I was minor, whereas masking of Ly49B was not detected. These data significantly extend the MHC-I specificity of Ly49 family receptors and show that the accessibility of most, but not all, MHC-I-binding Ly49 receptors is modulated by the expression of MHC-I in cis.

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Section: Ly49b and Ly49qmentioning

confidence: 99%

Interactions of Ly49 Family Receptors with MHC Class I Ligands in trans and cis

Scarpellino

Oeschger

Guillaume

et al. 2007

The Journal of Immunology

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“…Ly49Q is expressed neither on NK nor NKT cells, but on plasmacytoid dendritic cells (DCs), macrophages, and neutrophils. 7,9,10 The expression of Ly49Q appears to be regulated during the maturation of these cells and is significantly up-regulated by IFN-␥ treatment. 7,10,11 Ly49Q can associate with both Src homology 2-containing protein tyrosine phosphatase (SHP)-1 and SHP-2 in a tyrosine phosphorylation-dependent manner.…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q

Yoshizaki

Tazawa

Kasumi

et al. 2009

Blood

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Toll-like receptor (TLR) 9 recognizes unmethylated microorganismal cytosine guanine dinucleotide (CpG) DNA and elicits innate immune responses. However, the regulatory mechanisms of the TLR signaling remain elusive. We recently reported that Ly49Q, an immunoreceptor tyrosine-based inhibitory motif-bearing inhibitory receptor belonging to the natural killer receptor family, is crucial for TLR9-mediated type I interferon production by plasmacytoid dendritic cells. Ly49Q is expressed in plasmacytoid dendritic cells, macrophages, and neutrophils, but not natural killer cells. In this study, we showed that Ly49Q regulates TLR9 signaling by affecting endosome/ lysosome behavior. Ly49Q colocalized with CpG in endosome/lysosome compartments. Cells lacking Ly49Q showed a disturbed redistribution of TLR9 and CpG. In particular, CpG-induced tubular endolysosomal extension was impaired in the absence of Ly49Q. Consistent with these findings, cells lacking Ly49Q showed impaired cytokine production in response to CpG-oligodeoxynucleotide. Our data highlight a novel mechanism by which TLR9 signaling is controlled through the spatiotemporal regulation of membrane trafficking by the immunoreceptor tyrosinebased inhibitory motif-bearing receptor Ly49Q. (Blood. 2009;114:1518-1527)

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“…In the literature, murine Ly49Q has been reported to be expressed on cDCs and pDCs and has been suggested to regulate their functions (21,26). It has also been reported that human thymic pDCs regulate the nTreg developmental process (9,10).…”

Section: Figurementioning

confidence: 99%

“…On encountering MHC class I molecules, they transmit inhibitory signals to prevent NK cells from mediating cytotoxicity (17). At present, it is known that some members of the Ly49 family transmit activating, instead of inhibitory, signals and some are expressed on T cells and DCs and perform distinct functions (18)(19)(20)(21)(22). On the basis of the structural characteristics of Ly49s3-that is, the presence of a positively charged arginine residue in the transmembrane domain for association with adaptor proteins containing immunoreceptor tyrosinebased activating motifs-it has been predicted to be an activating receptor.…”

Section: Loss Of Ly49s3 Gene Expression In Hhr Thymic Cdcsmentioning

confidence: 99%

Lectin-like Receptor Ly49s3 on Dendritic Cells Contributes to the Differentiation of Regulatory T Cells in the Rat Thymus

Yamada

Nanashima

Akita

et al. 2013

The Journal of Immunology

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Naturally occurring regulatory T cells (nTregs), important for immune regulation and the maintenance of self-tolerance, develop in the thymus. The Hirosaki hairless rat (HHR), derived from the Sprague–Dawley rat (SDR), was shown to have decreased peripheral lymphocyte number, small thymus, and leukocyte infiltration in its dermis. In the HHR thymus, the medulla was underdeveloped and nTreg number was decreased. Array comparative genome hybridization revealed the deletion of an NK cell lectin-like receptor gene, Ly49s3, detecting MHC class I molecules on target cells, in the chromosome 4q42 region in HHRs. The gene was expressed in thymic conventional dendritic cells (cDCs) in SDRs, but not in HHRs. When CD4–single-positive or CD4+CD8−CD25− thymocytes were cultured with thymic cDCs, the expression of nTreg marker genes was lower when these cells were from HHRs than from SDRs, suggesting that HHR cDCs are deficient in the ability to induce and maintain nTreg differentiation. Expression of the genes was recovered when Ly49s3 was expressed on HHR thymic cDCs. Expression levels of MHC class II genes, presumably from cDCs, were parallel to those of nTreg marker genes in mixed-cell cultures. However, in the presence of an anti-MHC class I Ab, blocking interaction between Ly49s3 and MHC class I molecules, the expression of the former genes was upregulated, whereas the latter was downregulated. These results suggest that Ly49s3 contributes to nTreg regulation along with MHC class II molecules, whose effects alone are insufficient, and loss of Ly49s3 from thymic cDCs is the reason for the nTreg deficiency in HHRs.

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Inhibitory NK Receptor Ly49Q Is Expressed on Subsets of Dendritic Cells in a Cellular Maturation- and Cytokine Stimulation-Dependent Manner

Cited by 43 publications

References 48 publications

Interactions of Ly49 Family Receptors with MHC Class I Ligands in trans and cis

Interactions of Ly49 Family Receptors with MHC Class I Ligands in trans and cis

Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q

Lectin-like Receptor Ly49s3 on Dendritic Cells Contributes to the Differentiation of Regulatory T Cells in the Rat Thymus

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