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IMAI Masaki

    Graduate School of Medical Sciences Department of Immunology　Lecturer
Contact： imaimmed.nagoya-cu.ac.jp
Last Updated :2024/04/26

Researcher Information

J-Global ID

Research Areas

  • Life sciences / Immunology

Academic & Professional Experience

  • 2023/04 - Today  Kyoto Tachibana University健康科学部臨床検査学科教授
  • 2008/01 - 2023/03  Nagoya City UniversityGraduate School of Medical Sciences, Department of Immunology講師
  • 2006/06 - 2007/12  Osaka Dental University薬理学講座講師
  • 2003/09 - 2006/05  Medical University pf South CarolineDept. fo Microbiology & ImmunologyResearch Assistant Professor
  • 2001/04 - 2003/08  アメリカ・サウスカロライナ医科大学微生物免疫学博士研究員

Published Papers

Books etc

  • 補体への招待
    メジカルビュー社 2011

MISC

Awards & Honors

  • 2023/08 日本補体学会 日本補体学会優秀賞
  • 2004 The Medical University of South Carolina Institutional Research Funds of 2004-05・New Investigator Grant Award
     
    受賞者: IMAI Masaki

Research Grants & Projects

  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2022/04 -2026/03 
    Author : 的場 拓磨; 岩崎 真一; 川北 大介; 今井 優樹
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2020/04 -2023/03 
    Author : 今井 優樹; 志馬 寛明
     
    抗腫瘍免疫応答の抑制に中心的な働きを担うTregに対してC3aRおよびC5aRがどのように作用するかは未だに明らかでない。そこで本研究でヒト口腔癌においてC3aRおよびC5aRがどのようにTregを活性化し、抗腫瘍免疫を制御しているのかの解明を試みた。昨年度は、公開されている頭頸部癌のデータベースを用い、Tregのマスター転写Foxp3 とC3aRおよびC5aRの発現レベル解析したところ、C3aRとC5aRのmRNA発現はともにFoxp3の発現が強く相関することを明らかにした。 今年度はヒト頭頸部がん浸潤細胞のフローサイトメーター解析を行った。ヒト頭頸部がん浸潤TregのC3aRおよびC5aRの発現はほとんど検出できず、CD4+T細胞も同様であった。また、頭頸部がんのシングルセルRNAシークエンスの公開データベースを用いて頭頸部がん浸潤細胞免疫細胞の解析を行ったところ、TregにはC3aRは一部の細胞に発現が検出できたが、C5aRはフローサイトメーター解析と同様にほとんど検出できず、これらのレセプターの発現は正常組織から採取されたTregと比較しても差は見られなかった。さらにC5aRの遺伝子発現はCD4+T細胞、CD8+T細胞、B細胞などのリンパ球でもほとんど発現していなかった。この結果から口腔癌浸潤Tregが補体系によってダイレクトに活性化されてはおらず、他の細胞によって間接的に活性化されていることが明らかになった。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2019/10 -2023/03 
    Author : 山崎 小百合; 今井 優樹; 的場 拓磨; 志馬 寛明; 浦木 隆太
     
    自己免疫疾患は、自己と非自己を区別する免疫学的自己寛容のシステムが破綻し、本来であれば自己を攻撃しない免疫システムが自己を攻撃することにより発症する。免疫学的自己寛容の維持は、多くの仕組みで維持されているが、何らかの要因で破綻し、その結果、自己免疫疾患が発症する。自己免疫疾患の発症のメカニズムは、不明な点が多いが、その誘因の一つとして、病巣感染がどのようにして自己免疫疾患を誘因するか、その詳細な病態メカニズムの解明を目指し、これまでの私たちの研究成果を発展させて、各専門分野の先端研究者である海外共同研究者と協力し、病巣感染の病態メカニズムに迫ることを目指す。将来、発症メカニズムに基づいた副作用、合併症のおきにくい治療法の開発への貢献を目指し、新たな病巣感染のモデルも導入し、実験を進めており、現在解析中である。準備実験、条件決定に加え、シングルセルRNA-シークエンスなどのパブリックデータベース解析も利用した解析も行なっている。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2019/04 -2022/03 
    Author : Shime Hiroaki
     
    CD4-positive Fopx3-positive regulatory T cells (Tregs) are selectively accumulated in the ultraviolet (UV)-irradiated skin. Gene expression of UV-expanded skin Treg cells was compared with that of Treg cells or conventional T (Tconv) cells in lymph nodes and other tissues. We identified a specific pattern of gene expression in UVB-expanded skin Treg cells and found that they promote skin wound healing by producing proenkephalin (PENK) and amphiregulin (AREG) to promote proliferation and motility of keratinocytes.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2018/04 -2022/03 
    Author : OHTA RIEKO
     
    In cancer patients, despite the expression of cancer-specific antigens in cancer tissue, serum antibody titers against cancer are low and the frequency of cancer-specific cytotoxic T cells (CTL, killer T cells) is low. In this study, we demonstrated the potential for in vitro affinity maturation of HLA-A24-restricted, which are present in approximately 60% of the Japanese population, cancer antigen-specific CTL clones using the 'method of TCR display system using 293T cells '. We were also able to construct a single chain variable fragment (scFv) that induces the formation of membrane attack complexes. Linking this scFv with high-affinity TCR mutants could lead to the development of new therapeutic reagents.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2017/04 -2020/03 
    Author : Imai Masaki
     
    C5a receptor (C5aR) is overexpressed in many cancer tissues, and binding of C5a to C5aR causes cancer growth, invasion and metastasis. We first examined whether C5aR expresses of the oral cancer cell lines or not, mRNA level of C5aR was highly detected. On the other hand, it has been reported that the C5a-C5aR system induces the differentiation of regulatory T cells (Treg cells) and invasion of Treg cells into cancer tissues. However, despite the reports that the C5a-C5aR system acts Treg cells, expression level of C5aR was very low on Treg cells.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2016/04 -2019/03 
    Author : Yamazaki Sayuri; MORITA Akimichi
     
    We showed that antigen presentation by dendritic cells expand antigen-specific regulatory T cells and that dendritic cell-expanded regulatory T cells suppress autoimmunity and graft-versus host disease in a specific way using mice. Based on these our former reports, we performed experiments to control antigen specificity of regulatory T cells using murine and human dendritic cells. In this project in the past three years, we were able to report several findings including a dendritic subset to expand regulatory T cells specifically and its gene expressions.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2016/04 -2018/03 
    Author : Odanaka Mizuyu
     
    Ultraviolet B (UVB) irradiation is known to induce immune tolerance. In this study, we investigated the roles of dendritic cells (DCs) subsets for UVB-mediated immune tolerance. We found that Langerin negative DCs but not LCs or Langerin positive dermal DCs are required for regulatory T cells (Tregs) expansion in UVB-exposed skin. Upon UVB exposure, CD11b-type Langerin negative DCs upregulated the expression of several tolerogenic genes related to Tregs function and proliferation. These results indicate that CD11b-type Langerin negative DCs from the UVB-exposed skin are specialized to expand Treg cells in the skin, which suppress autoimmunity.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2016/04 -2018/03 
    Author : Yamazaki Sayuri; MORITA Akimichi; OHKURA Naganari
     
    Immune checkpoint inhibitors such as anti-CTLA-4 Ab and anti-PD1 Ab are now available for melanoma, which is effective for some patients. We conducted this research to provide data that these immunotherapies can be also effective for skin rare cancers and other cancers that are not yet approved for the use of immune checkpoint inhibitors. First we determined sampling conditions such as usage of enzymes to digest tumors because samples were very valuable. We found that regulatory T cells infiltrated into skin rare cancers and other cancers by flowcytometry. We also found that the regulatory T cells expressed specific gene expression patterns.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2014/04 -2018/03 
    Author : Ohta Rieko
     
    Receptor for advanced glycation end products (RAGE) is expressed in 82% of oral squamous cell carcinoma (OSCC) patients. RAGE promotes cell proliferation, migration, invasion, and angiogenesis of OSCCs through various intracellular signals induced by high mobility group box-1 (HMGB1) or the like as a ligand. On the other hand, type I mucin MUC1 is well known as a cancer antigen, highly overexpressed and loses its polarized distribution on the surface of tumor cells. In this study, we produced monoclonal antibodies against RAGE, then designed to improve the single chain Fv (bi-scFv) binding to both RAGE and MUC1. The bi-scFv binding to RAGE and MUC1 might suppress tumor growth and provide particular benefits under conditions of intractable cancers, since RAGE and MUC1 are expressed in various cancers and RAGE signaling is important for tumor growth.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2014/04 -2017/03 
    Author : IMAI Masaki; MIZUNO Masashi
     
    To assess influence of periodontal disease-causing bacteria infection on peritoneal dialysis (PD), we investigated the relationship between periodontal pathogenic bacterial infection an the tissue damage associated with PD were examined. We tried to detect periodontitis causative bacteria in peritoneal dialysis from patients. However, P. gingivalis which is a periodontitis causing bacterium could not be detected. Next, rat C5a and C5adesArg were prepared in order to clarify in the model animals that bacterial infection and elevation of the concentration of anaphylatoxin directly exacerbate the inflammatory response. When C5a and C5adesArg were administered to rats, a marked inflammatory response was not detected with anaphylatoxin alone. As contrast, C5a administration with low concentration of LPS induced a strong inflammatory response. Interestingly, C5adesArg, that is inactivated C5a also enhanced inflammatory response when pre-administration of low concentration LPS.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2011 -2012 
    Author : IMAI MASAKI
     
    To conserve both form and function in the oral area, effective and selective drugs against oral cancer will be required. We focused on Cetuximab, that is indicated for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing cancer. Complement deposition (C3) on HSC4 (human oral squamous cell carcinomas cell line) by incubation with Cetuximab and human serum was slightly enhanced. On the other hands, complement inhibitors expressed on tumor cells provide a hindrance to the therapeutic efficacy of some monoclonal antibodies. We investigated a strategy to amplify complement activation on tumor cells and overwhelm complement inhibitor function. Complement deposition and lysis of HSC4 cells by incubation with Cetuximab and human serum was enhanced in the presence of CR2-Fc. CR2-Fc enhances the therapeutic efficacy of antibody therapy and may provide particular benefits under conditions of limiting antibody concentration or low tumor antigen density.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2010 -2012 
    Author : MAKIE Toshio; IMAI Masaki; KITATANI Kazuyuki; MORINAGA Osamu; NAKAMURA Tsuyoshi
     
    Information about a drug development is available at two sources, one is from the National Institution of Public Health and the other is the international clinical trial research platform managed by WHO. Finally all information of the clinical study is collected to the site managed by WHO. Almost all the information of Hepatitis type C was available from the portal site managed by WHO, whileonly a half of the information was available from the portal site of the domestic institution. We showed that the information of the drug development can be obtained more than two years earlier rather than waiting the publication of the study, using these sites.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2010 -2012 
    Author : OKADA Noriko; IMAI Masaki
     
    C5a anaphylatoxin is considered to be an effective target for treatment of hyperinflammation since C5a stimulates neutrophils and endothelial cells, then generation of tumor necrosis factor alpha (TNFα) and other inflammatory cytokines. To clear how C5a induces to serious inflammatory responses, we generated C5a inhibitory peptides with an evolutionary computer program that generates complementary peptide (C-pep) sequences. We showed that a novel C5a C-peptide, AcpepA significantly improved an injury score compared to PBS control on rat model with brain ischemia and reperfusion injury.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2009 -2010 
    Author : IMAI Masaki
     
    We have studied the anti-tumor activities of an anti-MUC1 antibody with oral squamous cell carcinoma (OSCC). We hypothesized the inhibition of complement regulatory proteins (CRPs) could enhance anti-tumor activity. Therefore, that reversing the effects of complement regulatory proteins expressed on a tumor cell surface will allow more effective immune-mediated clearance of tumor cells and improve prospects for successful immunotherapy. When the complement-dependent cytotoxicity was compared treatment with both an anti-MUC1 mAb and inhibiting mAbs of CD55 or CD59 to an anti-MUC1 mAb alone, a 2- to 3-fold increase in C-dependent cell lysis was observed, respectively. It was also proposed to produce the tri-functional antibodies recognized both MUC1 and CRPs. We done to produce the expression vectors of tri-functional antibodies.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2007 -2008 
    Author : IMAI Masaki
     
    エンドセリン受容体阻害ペプチドは乳ガン細胞SKBR3, MCF7細胞において60-70%の増殖抑制がみられたが、口腔癌では増殖阻害活性を示さなかった。これらの結果より、口腔癌の増殖においてエンドセリンA受容体の機能は重要でない可能性が示唆された。また、口腔癌特異的な抗原(MUC1)に対する特異抗体C595 の単独での作用を調べた。C595 は補体依存性細胞障害反応、抗体依存性細胞障害反応をわずかに誘導したが、抗体単独では細胞増殖抑制には影響がなかった。従って、MUC1特異的モノクローナル抗体は口腔癌の標的化には有効だが、抗体単独での抗体免疫療法では有効性が見られないことが明らかになった。

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