RP105 Is Associated With MD-1 and Transmits an Activation Signal in Human B Cells

Miura, Yoshiaki; Shimazu, Rintaro; Miyake, Kensuke; Akashi, Shigeo; Ogata, Hirotaka; Yamashita, Yoshio; Narisawa, Yutaka; Kimoto, Masao

doi:10.1182/blood.v92.8.2815

Cited by 115 publications

(68 citation statements)

References 19 publications

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“…Two other significantly repressed genes are LY64 and LY86. LY64, also known as RP105, was originally cloned as a B‐cell‐specific molecule and is able to drive B‐cell proliferation (Miura et al , 1998). LY64 is a specific homolog of TLR4.…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 4 signaling plays a role in triggering periodontal infection

Sun

Shu

Zhang

et al. 2008

FEMS Immunology &Amp; Medical Microbiology

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Toll-like receptors (TLRs) are a group of sensors on the surface of antigen-presenting cells, such as dendritic cells and macrophages, which recognize microbial pathogens and induce innate and adaptive immune responses. Periodontitis is an inflammatory disease characterized by the destruction of tooth-supporting structures. In order to address whether TLR4 signaling plays a role in periodontitis, we studied the gene expression change in human periodontal ligament cells (HPDLCs) in response to TLR4 ligand, lipopolysaccharide treatment by microarray analysis. Expression of TLR4 was detected in HPDLCs. Lipopolysaccharide treatment increased the expression of 12 genes (more than twofold), including TLR4, TLR5, TLR7, Pellino 1, colony stimulating factor 2 (CSF2) and IL-6. In addition, the expression of 15 genes (less than equal to twofold) was decreased, including Fos, LY64 and LY86. In addition, real-time PCR was used to confirm the change of gene expression of TLR4, IL-6 and Fos. We also showed that the upregulation of IL-6 by lipopolysaccharide treatment was TLR4-dependent. This pattern of gene expression indicates that pathogens may trigger TLR4 signaling and cause periodontitis. Manipulating TLR4 signaling may potentially become one of the recognized therapies for periodontitis.

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Section: Discussionmentioning

confidence: 99%

Toll-like receptor 4 signaling plays a role in triggering periodontal infection

Sun

Shu

Zhang

et al. 2008

FEMS Immunology &Amp; Medical Microbiology

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mentioning

confidence: 85%

“…Previous work from this and other laboratories suggested that the molecule MD‐1 was involved in the transmission of activation signals within lymphoid cells (12, 13). The molecule is thought to act by stabilizing expression of cell‐surface coreceptors which transmit signals leading to the activation of nuclear factor‐κB (NF‐κB) in APCs, which in turn can result in enhanced expression of the costimulatory molecules CD80/CD86 (12–15). We have shown in addition that functional blockade of MD‐1 expression results in decreased expression of these costimulatory molecules, prolongs both allogeneic and xenogeneic skin graft survival in mice, and prevents type‐1 cytokine‐induced fetal loss (12, 14, 16).…”

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confidence: 85%

MD‐1 expression regulates direct and indirect allorecognition

Hadidi

Gorczynski

2004

Tissue Antigens

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Expression of the molecule MD-1 was previously described to regulate allogeneic and xenogeneic skin graft survival, as documented by the decrease in rejection seen following functional blockade of MD-1 expression in vivo, using antisense oligodeoxynucleotides (ODNs) or anti-MD-1 antibodies. It was unclear from these data whether blockade of expression of MD-1 on donor or recipient cells was crucial. We have investigated the effect on allorecognition of treating skin graft donors, and/or recipients, of either fully major histocompatibility complex (MHC)-mismatched allogeneic skin grafts (C3H with C57BL/6 grafts and vice versa) or grafts differing at only multiple minor alloantigens (C3H with B10.BR grafts; C57BL/6 with C3H.SW), with antisense ODNs to MD-1, or in some cases, following transplantation of class II-deficient cells into class I-deficient mice. Graft-specific cytotoxic T lymphocytes (CTLs) were measured in spleen cells recovered at sacrifice of recipients and following donor-specific restimulation in vitro. In the latter case, we also measured cell proliferation and (by enzyme-linked immunosorbent assay) production of interleukin-2 (IL-2)/interferon-gamma (IFN-gamma) or IL-4/IL-10 in vitro (nominal type-1 vs type-2 cytokines). CTL responses to minor-incompatible grafts were diminished, only if graft recipients were treated with ODNs. However, treatment of graft donor and/or recipient of MHC-incompatible grafts produced inhibition of CTL production. Optimal inhibition came from treating both. Specific suppression of CTL production coincided with inhibition of proliferation and preferential production of IL-4 and IL-10 at the expense of IL-2 and IFN-gamma. Our data are consistent with the hypothesis that MD-1 expression regulates both the direct and indirect pathways of allorecognition and that regulation of MD-1 expression may thus help regulate clinical graft rejection.

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“…17). Anti-CD180 antibodies with a stimulatory function (MHR73-11) and without a stimulatory function (N2C1) were obtained from BioLegend and GeneTex, respectively (18,19). LPS, Pam3Csk, flagellin, poke weed mitogen, and SN-50 were dissolved in 0.9% NaCl.…”

Section: Reagentsmentioning

confidence: 99%

Myeloma Cells Are Activated in Bone Marrow Microenvironment by the CD180/MD-1 Complex, Which Senses Lipopolysaccharide

et al. 2018

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Multiple myeloma (MM) cells acquire dormancy and drug resistance via interaction with bone marrow stroma cells (BMSC) in a hypoxic microenvironment. Elucidating the mechanisms underlying the regrowth of dormant clones may contribute to further improvement of the prognosis of MM patients. In this study, we find that the CD180/MD-1 complex, a noncanonical lipopolysaccharide (LPS) receptor, is expressed on MM cells but not on normal counterparts, and its abundance is markedly upregulated under adherent and hypoxic conditions. Bacterial LPS and anti-CD180 antibody, but not other Toll-like receptor ligands, enhanced the growth of MM cells via activation of MAP kinases ERK and JNK in positive correlation with expression levels of CD180. Administration of LPS significantly increased the number of CD180/CD138 double-positive cells in a murine xenograft model when MM cells were inoculated with direct attachment to BMSC. Knockdown of CD180 canceled the LPS response and Promoter analyses identified IKZF1 (Ikaros) as a pivotal transcriptional activator of the gene. Both cell adhesion and hypoxia activated transcription of the gene by increasing Ikaros expression and its binding to the promoter region. Pharmacological targeting of Ikaros by the immunomodulatory drug lenalidomide ameliorated the response of MM cells to LPS in a CD180-dependent manner and Thus, the CD180/MD-1 pathway may represent a novel mechanism of growth regulation of MM cells in a BM milieu and may be a therapeutic target of preventing the regrowth of dormant MM cells. This study describes a novel mechanism by which myeloma cells are regulated in the bone marrow, where drug resistance and dormancy can evolve after treatment, with potential therapeutic implications for treating this often untreatable blood cancer. .

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RP105 Is Associated With MD-1 and Transmits an Activation Signal in Human B Cells

Cited by 115 publications

References 19 publications

Toll-like receptor 4 signaling plays a role in triggering periodontal infection

Toll-like receptor 4 signaling plays a role in triggering periodontal infection

MD‐1 expression regulates direct and indirect allorecognition

Myeloma Cells Are Activated in Bone Marrow Microenvironment by the CD180/MD-1 Complex, Which Senses Lipopolysaccharide

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