Updated on 2025/06/26

Information

 

写真a

 
MUNEMURA RYUSUKE
 
Organization
Faculty of Dental Science Department of Dental Science Assistant Professor
Graduate School of Dental Science Department of Dental Science（Concurrent）
School of Dentistry Department of Dentistry（Concurrent）
Title
Assistant Professor
Contact information
メールアドレス
Tel
0926426447
Profile
研究：IgG4関連疾患の病態形成に関与すると考えられる濾胞性ヘルパーT細胞について研究を行なっている。IgG４関連疾患において特異的なIL10+LAG3+Tfh細胞に着目して病態解明に向けて研究を進めている。 教育：研修医の臨床指導、学生の臨床実習指導を行なっている。また、学部学生のオスキーの実行委員として実務を行なっている。 臨床：九州大学病院顎口腔外科の病棟勤務を行なっており、副病棟医長として診療および病棟のマネージメントを行なっている。
Homepage

Research Areas

  • Life Science / Surgical dentistry

Research History

  • Kyushu University 九州大学大学院歯学研究院　口腔顎顔面病態学講座　顎顔面腫瘍制御学分野 Assistant Professor 

    2024.4

Education

  • Kyushu University   歯学部  

    2010.4 - 2016.3

Research Interests・Research Keywords

  • Research theme： Etiology of IgG4-related disease

    Keyword： IgG4-related disease, Tfh cells

    Research period： 2018.4 - 2024.3

Awards

  • 九大歯学優秀研究者賞

    2024.2   九州大学歯学研究院  

  • 日本シェーグレン症候群学会奨励賞

    2023.9   日本シェーグレン症候群学会  

  • 優秀ポスター発表賞

    2019.10   日本口腔外科学会  

Papers

  • Distinct disease-specific Tfh cell populations in two different fibrotic diseases: IgG4-related disease and Kimura’s disease Reviewed International journal

    Ryusuke Munemura, TAKASHI MAEHARA, Yuka Murakami, Risako Koga, Ryuichi Aoyagi, Naoki Kaneko, Atsushi Doi, Cory A. Perugino, Emanuel Della-Torre, Takako Saeki, Yasuharu Sato, Hidetaka Yamamoto, Tamotsu Kiyoshima, John H. Stone, Shiv Pillai, Seiji Nakamura.

    The Journal of Allergy and Clinical Immunology   2022.3

    　More details

    Language：English   Publishing type：Research paper (scientific journal)  

  • Granzyme K- and amphiregulin-expressing cytotoxic T cells and activated extrafollicular B cells are potential drivers of IgG4-related disease

    Koga, R; Maehara, T; Aoyagi, R; Munemura, R; Murakami, Y; Doi, A; Kono, M; Yamamoto, H; Niiro, H; Kiyoshima, T; Tanabe, M; Nakano, T; Matsukuma, Y; Kawano, M; Stone, JH; Pillai, S; Nakamura, S; Kawano, S

    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY   153 ( 4 )   1095 - 1112   2024.4   （ ISSN:0091-6749 eISSN:1097-6825 ）

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    Language：English   Publisher：Journal of Allergy and Clinical Immunology  

    Background: IgG4-related disease (IgG4-RD), an example of a type I immune disease, is an immune-mediated fibrotic disorder characterized by dysregulated resolution of severe inflammation and wound healing. However, truly dominant or pathognomonic autoantibodies related to IgG4-RD are not identified. Objective: We sought to perform single-cell RNA sequencing and T-cell receptor and B-cell receptor sequencing to obtain a comprehensive, unbiased view of tissue-infiltrating T and B cells. Methods: We performed unbiased single-cell RNA-sequencing analysis for the transcriptome and T-cell receptor sequencing and B-cell receptor sequencing on sorted CD3<sup>+</sup> T or CD19<sup>+</sup> B cells from affected tissues of patients with IgG4-RD. We also conducted quantitative analyses of CD3<sup>+</sup> T-cell and CD19<sup>+</sup> B-cell subsets in 68 patients with IgG4-RD and 30 patients with Sjögren syndrome. Results: Almost all clonally expanded T cells in these lesions were either Granzyme K (GZMK)-expressing CD4<sup>+</sup> cytotoxic T cells or GZMK<sup>+</sup>CD8<sup>+</sup> T cells. These GZMK-expressing cytotoxic T cells also expressed amphiregulin and TGF-β but did not express immune checkpoints, and the tissue-infiltrating CD8<sup>+</sup> T cells were phenotypically heterogeneous. MKI67<sup>+</sup> B cells and IgD<sup>−</sup>CD27<sup>−</sup>CD11c<sup>−</sup>CXCR5<sup>−</sup> double-negative 3 B cells were clonally expanded and infiltrated affected tissue lesions. GZMK<sup>+</sup>CD4<sup>+</sup> cytotoxic T cells colocalized with MKI67<sup>+</sup> B cells in the extrafollicular area from affected tissue sites. Conclusions: The above-mentioned cells likely participate in T-B collaborative events, suggesting possible avenues for targeted therapies. Our findings were validated using orthogonal approaches, including multicolor immunofluorescence and the use of comparator disease groups, to support the central role of cytotoxic CD4<sup>+</sup> and CD8<sup>+</sup> T cells expressing GZMK, amphiregulin, and TGF-β in the pathogenesis of inflammatory fibrotic disorders.

    DOI： 10.1016/j.jaci.2023.11.916

    Web of Science

    Scopus

    PubMed

  • Single-cell transcriptomics reveals granzyme K-expressing cytotoxic Tfh cells in tertiary lymphoid structures in IgG4-RD

    Aoyagi, R; Maehara, T; Koga, R; Munemura, R; Tomonaga, T; Murakami, Y; Doi, A; Yamamoto, H; Kiyoshima, T; Kawano, S; Nakamura, S

    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY   153 ( 2 )   513 - 520.e10   2024.2   （ ISSN:0091-6749 eISSN:1097-6825 ）

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    Language：English   Publisher：Journal of Allergy and Clinical Immunology  

    Background: Germinal center (GC) responses controlled by T follicular helper (Tfh) and T follicular regulatory (Tfr) cells are crucial for the generation of high-affinity antibodies. Acquired immune responses to tissue-released antigens might be mainly induced in tertiary lymphoid organs (TLOs) with GCs in affected tissues. IgG4-related disease (IgG4-RD) demonstrates polarized isotype switching and TLOs in affected tissues. We performed single-cell transcriptomics of tissue-infiltrating T cells from these TLOs to obtain a comprehensive, unbiased view of tissue-infiltrating GC-Tfh cells. Objective: To identify GC-Tfh-cell subsets in TLOs in patients with IgG4-RD using single-cell transcriptomics. Methods: Single-cell RNA sequencing of sorted CD3<sup>+</sup> T cells and multicolor immunofluorescence analysis were used to investigate CD4<sup>+</sup>CXCR5<sup>+</sup>Bcl6<sup>+</sup> GC-Tfh cells in affected lesions from patients with IgG4-RD. Results: Infiltrating CD4<sup>+</sup>CXCR5<sup>+</sup>Bcl6<sup>+</sup> Tfh cells were divided into 5 main clusters. We detected HLA<sup>+</sup> granzyme K<sup>+</sup> (GZMK<sup>+</sup>) Tfh cells with cytotoxicity-associated features in patients with IgG4-RD. We also observed abundant infiltrating Tfr cells with suppressor-associated features in patients with IgG4-RD. These GZMK<sup>+</sup> Tfh cells and Tfr cells clustered together in affected tissues from patients with IgG4-RD. Conclusions: This single-cell data set revealed a novel subset of HLA<sup>+</sup>GZMK<sup>+</sup> cytotoxic Tfh cells infiltrating affected organs in patients with IgG4-RD, suggesting that infiltrating Tfr cells might suppress cytotoxic Tfh cells.

    DOI： 10.1016/j.jaci.2023.08.019

    Web of Science

    Scopus

    PubMed

  • Granzyme K- and amphiregulin-expressing cytotoxic T cells and activated extrafollicular B cells are potential drivers of IgG4-related disease. Reviewed International journal

    Risako Koga, Takashi Maehara, Ryuichi Aoyagi, Ryusuke Munemura, Yuka Murakami, Atsushi Doi, Michihito Kono, Hidetaka Yamamoto, Hiroaki Niiro, Tamotsu Kiyoshima, Mika Tanabe, Toshiaki Nakano, Yuta Matsukuma, Mitsuhiro Kawano, John H Stone, Shiv Pillai, Seiji Nakamura, Shintaro Kawano.

    The Journal of Allergy and Clinical Immunology   2023.11

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    Language：English   Publishing type：Research paper (scientific journal)  

  • Single-cell transcriptomics reveals granzyme K-expressing cytotoxic Tfh cells in tertiary lymphoid structures in IgG4-RD. Reviewed International journal

    Ryuichi Aoyagi, Takashi Maehara, Risako Koga, Ryusuke Munemura, Tadashi Tomonaga, Yuka Murakami, Atsushi Doi, Hidetaka Yamamoto , Tamotsu Kiyoshima, Shintaro Kawano, Seiji Nakamura.

    The Journal of Allergy and Clinical Immunology   2023.8

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    Language：English   Publishing type：Research paper (scientific journal)  

  • Cytotoxic CD8<SUP>+</SUP> T cells may be drivers of tissue destruction in Sjogren's syndrome

    Kaneko, N; Chen, H; Perugino, CA; Maehara, T; Munemura, R; Yokomizo, S; Sameshima, J; Diefenbach, TJ; Premo, KR; Chinju, A; Miyahara, Y; Sakamoto, M; Moriyama, M; Stone, JH; Nakamura, S; Pillai, S

    SCIENTIFIC REPORTS   12 ( 1 )   15427   2022.9   （ ISSN:2045-2322 ）

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    Language：English   Publisher：Scientific Reports  

    Sjögren’s syndrome is a chronic autoimmune disorder whose pathogenesis is poorly understood and that lacks effective therapies. Detailed quantitative and spatial analyses of tissues affected by Sjögren’s syndrome were undertaken, including the quantitation of the frequency of selected cell–cell interactions in the disease milieu. Quantitative analyses of CD4<sup>+</sup> T cell subsets and of CD8<sup>+</sup> T cells in the labial salivary glands from untreated patients with primary Sjögren’s syndrome revealed that activated CD8<sup>+</sup> cytotoxic T cells (CD8<sup>+</sup>CTLs) were the most prominent T cells in these infiltrates. An accumulation of apoptotic glandular epithelial cells, mainly ductal and acinar cells, was observed, consistent with the impaired salivary secretion often observed in patients with this disease. FasL expressing activated CD8<sup>+</sup> T cells were seen to accumulate around Fas expressing apoptotic epithelial cells. Quantitative analyses of apoptotic cell types and of conjugates between cytotoxic T cells and epithelial cells undergoing apoptosis suggest that Sjögren’s syndrome is primarily driven by CD8<sup>+</sup>CTL mediated execution of epithelial cells mainly represented by ductal and acinar cells.

    DOI： 10.1038/s41598-022-19397-w

    Web of Science

    Scopus

    PubMed

  • Distinct disease-specific Tfh cell populations in 2 different fibrotic diseases: IgG4-related disease and Kimura disease

    Munemura, R; Maehara, T; Murakami, Y; Koga, R; Aoyagi, R; Kaneko, N; Doi, A; Perugino, CA; Della -Torre, E; Saeki, T; Sato, Y; Yamamoto, H; Kiyoshima, T; Stone, JH; Pillai, S; Nakamura, S

    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY   150 ( 2 )   440 - +   2022.8   （ ISSN:0091-6749 eISSN:1097-6825 ）

    　More details

    Language：English   Publisher：Journal of Allergy and Clinical Immunology  

    Background: How T follicular (Tfh) cells contribute to many different B-cell class-switching events during T-cell–dependent immune responses has been unclear. Diseases with polarized isotype switching offer a unique opportunity for the exploration of Tfh subsets. Secondary and tertiary lymphoid organs in patients with elevated tissue expression levels of IgE (Kimura disease, KD) and those of IgG<inf>4</inf> (IgG<inf>4</inf>-related disease, IgG<inf>4</inf>-RD) can provide important insights regarding cytokine expression by Tfh cells. Objective: We sought to identify disease-specific Tfh cell subsets in secondary and tertiary lymphoid organs expressing IL-10 or IL-13 and thus identify different cellular drivers of class switching in 2 distinct types of fibrotic disorders: allergic fibrosis (driven by type 2 immune cells) and inflammatory fibrosis (driven by cytotoxic T lymphocytes). Methods: Single-cell RNA sequencing, in situ sequencing, and multicolor immunofluorescence analysis were used to investigate B cells, Tfh cells, and infiltrating type 2 cells in lesion tissues from patients with KD or IgG<inf>4</inf>-RD. Results: Infiltrating Tfh cells in tertiary lymphoid organs from IgG<inf>4</inf>-RD were divided into 6 main clusters. We encountered abundant infiltrating IL-10–expressing LAG3<sup>+</sup> Tfh cells in patients with IgG<inf>4</inf>-RD. Furthermore, we found that infiltrating AICDA<sup>+</sup>CD19<sup>+</sup> B cells expressing IL-4, IL-10, and IL-21 receptors correlated with IgG<inf>4</inf> expression. In contrast, we found that infiltrating IL-13–expressing Tfh cells were abundant in affected tissues from patients with KD. Moreover, we observed few infiltrating IL-13–expressing Tfh cells in tissues from patients with IgG<inf>4</inf>-RD, despite high serum levels of IgE (but low IgE in the disease lesions). Cytotoxic T cells were abundant in IgG<inf>4</inf>-RD; in contrast, type 2 immune cells were abundant in KD. Conclusions: Our analysis revealed a novel subset of IL-10<sup>+</sup>LAG3<sup>+</sup> Tfh cells infiltrating the affected organs of IgG<inf>4</inf>-RD patients. In contrast, IL-13<sup>+</sup> Tfh cells and type 2 immune cells infiltrated those of KD patients.

    DOI： 10.1016/j.jaci.2022.03.034

    Web of Science

    Scopus

    PubMed

  • Distinct disease-specific Tfh cell populations in two different fibrotic diseases: IgG4-related disease and Kimura's disease. Reviewed International coauthorship

    Nakamura Seiji

    Journal of Allergy and Clinical Immunology   in press   2022

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  • Tissue-infiltrating immune cells contribute to understanding the pathogenesis of Kimura's Disease: a case report Reviewed International journal

    Takashi Maehara, Ryusuke Minemura, Mayumi Shimizu, Noriko Kakizoe, Naoki Kaneko, Moriyama Masafumi, Yuka Murakami, Tamotsu Kiyoshima, Shintaro Kawano, Seiji Nakamura.

    Medicine   2019.11

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    Language：English   Publishing type：Research paper (scientific journal)  

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Presentations

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MISC

  • IgG4関連疾患の病態にかかわるT細胞とB細胞

    前原 隆, 古賀 茉莉奈, 古賀 理紗子, 張 玲, 青柳 龍一, 宗村 龍祐, 中村 誠司, Pillai Shiv, 川野 真太郎

    臨床免疫・アレルギー科   82 ( 6 )   635 - 644   2024.12   （ ISSN:1881-1930 ）

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    Language：Japanese   Publisher：(有)科学評論社  

  • IgG4関連疾患と木村病における疾患特異的な濾胞性T細胞

    前原 隆, 宗村 龍祐, 古賀 理紗子, 中村 誠司

    臨床免疫・アレルギー科   79 ( 3 )   339 - 347   2023.3   （ ISSN:1881-1930 ）

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    Language：Japanese   Publisher：(有)科学評論社  

  • 新規疾患概念；IgG4関連疾患の免疫学的特徴から病態解明へのアプローチ Reviewed

    前原隆、宗村龍祐、村上祐香

    アレルギーの臨床   2020.9

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Professional Memberships

  • 日本口腔外科学会

  • 日本シェーグレン学会

  • IgG4関連疾患学会

  • 日本口腔科学会

Research Projects

  • シェーグレン症候群の病態形成に関与する特異的なT、B細胞の同定

    Grant number：25K20377  2025.4 - 2028.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    宗村 龍祐

    　 More details

    Grant type：Scientific research funding

    シェーグレン症候群（SjS）は、唾液腺や涙腺などの外分泌腺が特異的に障害を受ける臓器特異的自己免疫疾患である。病理学的特徴として、罹患臓器である腺組織に自己反応性CD4+T 細胞と B 細胞が集積し、T・B 細胞の相互連関から特異な免疫ネットワークの破綻が生じ、腺組織の組織傷害が生じている。しかしその病態の詳細は未だ不明なため、ステロイドや唾液分泌促進などの対症療法に終始するのが現状で、有効な治療法がない。本研究では、SjS 患者の罹患臓器および末梢血より病因 T・B 細胞について明らかにし、それらを標的とした新規治療法の確立を目指す。

    CiNii Research

  • IgG4関連疾患におけるクラススイッチ機構の解析

    Grant number：21K21090  2021.8 - 2025.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Research Activity Start-up

    宗村 龍祐

    　 More details

    Grant type：Scientific research funding

    IgG4 関連疾患 （ IgG4-RD ） はB 細胞の免疫グロブリンの産生がIgG4 へクラススイッチする特異的な全身性の疾患である。未だIgG4 産生の病態は不明であり、治療法が確立されていない。従前に我々はIgG4 産生に関与する疾患特異的な細胞群を探索する目的に、IgG4-RD 患者の罹患臓器に浸潤した全免疫細胞をシングルセルレベルで解析した結果、極めて特徴的なIgG4 産生 B 細胞および濾胞性ヘルパー T (Tfh)細胞の存在を明らかにした。そこで本研究では、IgG4 産生の分子機序を明らかにし、IgG4 産生に関与する疾患特異的な細胞群を標的とした新規治療法の確立を目指す。

    CiNii Research

  • 歯科患者を対象とした歯科用局所麻酔剤アルチカイン塩酸塩・アド レナリン酒石酸水素塩注射剤のリドカイン塩酸塩・アドレナリン酒 石酸水素塩注射剤を対照とする第Ⅲ相多施設共同単盲検非劣性試験

    2021.4 - 2022.3

  • IgG4関連疾患におけるクラススイッチ機構の解析

    2021 - 2024

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Research Activity start-up

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    Authorship：Principal investigator  Grant type：Scientific research funding

Educational Activities

  • 研修医臨床指導

    令和6年4月より福岡医健専門学校（歯科衛生士）、九州医療専門学校（柔道整復師科）の非常勤講師を務めている。

Class subject

  • リサーチエクスポージャー

    2024.4 - 2025.6  

  • problem based learning（PBL）

    2024.4 - 2024.9   First semester

FD Participation

  • 2024.6   Role：Participation   Title：本学の国家試験への取り組み

    Organizer：[Undergraduate school/graduate school/graduate faculty]

Visiting, concurrent, or part-time lecturers at other universities, institutions, etc.

  • 2025  福岡医健専門学校歯科衛生士科   Classification:Part-time lecturer  Domestic/International Classification:Japan 

  • 2025  九州医療専門学校柔道整復師科   Classification:Part-time lecturer  Domestic/International Classification:Japan 

  • 2024  九州医療専門学校柔道整復師科  Classification:Part-time lecturer  Domestic/International Classification:Japan 

  • 2024  福岡医健専門学校歯科衛生士科  Classification:Part-time lecturer  Domestic/International Classification:Japan 

Other educational activity and Special note

  • 2025  Lecture at Education Method and Practice  学内の OSCE 実施委員会の委員を務めている

  • 2024  Special Affairs  学内の OSCE 実施委員会の委員を務めている

    　詳細を見る

    学内の OSCE 実施委員会の委員を務めている

  • 2023  Special Affairs  医療系大学間共用試験実施評価機構主催の2023年度歯学系臨床実習後臨床能力試験（CSX）認定評価者養成ワークショップに参加し、臨床能力試験臨床実地試験（CSX）認定評価者として認定された。

    　詳細を見る

    医療系大学間共用試験実施評価機構主催の2023年度歯学系臨床実習後臨床能力試験（CSX）認定評価者養成ワークショップに参加し、臨床能力試験臨床実地試験（CSX）認定評価者として認定された。

Outline of Social Contribution and International Cooperation activities

  • 学外の医療系専門学校における講義、開業歯科医院での口腔外科手術指導

Social Activities

  • 不明

    九州医療専門学校  2024.4

    　More details

    Audience：General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Other

  • 不明

    福岡医健専門学校  2024.4

    　More details

    Audience：General,　Scientific,　Company,　Civic organization,　Governmental agency

    Type：Other

Specialized clinical area

  • Biology / Medicine, Dentistry and Pharmacy / Dentistry / Surgical Dentistry

Clinician qualification

  • Certifying physician

    日本口腔外科学会

Year of medical license acquisition

  • 2016