本田 賢也 (ホンダ ケンヤ)

Honda, Kenya

写真a

所属(所属キャンパス)

医学部 微生物学・免疫学教室 (信濃町)

職名

教授

メールアドレス

メールアドレス

HP

特記事項

微生物学免疫学教室

経歴 【 表示 / 非表示

  • 1997年04月
    -
    2001年03月

    京都大学大学院, 医学系研究科分子遺伝学講座, 大学院生

  • 2001年04月
    -
    2007年03月

    東京大学, 医学部・医学系研究科免疫学講座, 助手

  • 2007年04月
    -
    2009年11月

    大阪大学大学院, 医学系研究科・免疫制御学, 准教授

  • 2009年12月
    -
    2015年03月

    東京大学, 医学部・医学系研究科・免疫学講座, 准教授

  • 2013年04月
    -
    継続中

    理化学研究所, 統合生命医科学研究センター 消化管恒常性研究チーム, チームリーダー

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学位 【 表示 / 非表示

  • 博士(医学), 京都大学大学院医学研究科, 2001年03月

 

論文 【 表示 / 非表示

  • IL-10 produced by macrophages regulates epithelial integrity in the small intestine

    Morhardt T., Hayashi A., Ochi T., Quirós M., Kitamoto S., Nagao-Kitamoto H., Kuffa P., Atarashi K., Honda K., Kao J., Nusrat A., Kamada N.

    Scientific Reports (Scientific Reports)  9 ( 1 )  2019年12月

     概要を見る

    © 2019, The Author(s). Macrophages (Mϕs) are known to be major producers of the anti-inflammatory cytokine interleukin-10 (IL-10) in the intestine, thus playing an important role in maintaining gastrointestinal homeostasis. Mϕs that reside in the small intestine (SI) have been previously shown to be regulated by dietary antigens, while colonic Mϕs are regulated by the microbiota. However, the role which resident Mϕs play in SI homeostasis has not yet been fully elucidated. Here, we show that SI Mϕs regulate the integrity of the epithelial barrier via secretion of IL-10. We used an animal model of non-steroidal anti-inflammatory drug (NSAID)-induced SI epithelial injury to show that IL-10 is mainly produced by MHCII+ CD64+ Ly6Clow Mϕs early in injury and that it is involved in the restoration of the epithelial barrier. We found that a lack of IL-10, particularly its secretion by Mϕs, compromised the recovery of SI epithelial barrier. IL-10 production by MHCII+ CD64+ Ly6Clow Mϕs in the SI is not regulated by the gut microbiota, hence depletion of the microbiota did not influence epithelial regeneration in the SI. Collectively, these results highlight the critical role IL-10-producing Mϕs play in recovery from intestinal epithelial injury induced by NSAID.

  • Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis

    Nakamoto N., Sasaki N., Aoki R., Miyamoto K., Suda W., Teratani T., Suzuki T., Koda Y., Chu P., Taniki N., Yamaguchi A., Kanamori M., Kamada N., Hattori M., Ashida H., Sakamoto M., Atarashi K., Narushima S., Yoshimura A., Honda K., Sato T., Kanai T.

    Nature Microbiology (Nature Microbiology)  4 ( 3 ) 492 - 503 2019年03月

     概要を見る

    © 2019, The Author(s), under exclusive licence to Springer Nature Limited. Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease and its frequent complication with ulcerative colitis highlights the pathogenic role of epithelial barrier dysfunction. Intestinal barrier dysfunction has been implicated in the pathogenesis of PSC, yet its underlying mechanism remains unknown. Here, we identify Klebsiella pneumonia in the microbiota of patients with PSC and demonstrate that K. pneumoniae disrupts the epithelial barrier to initiate bacterial translocation and liver inflammatory responses. Gnotobiotic mice inoculated with PSC-derived microbiota exhibited T helper 17 (T H 17) cell responses in the liver and increased susceptibility to hepatobiliary injuries. Bacterial culture of mesenteric lymph nodes in these mice isolated K. pneumoniae, Proteus mirabilis and Enterococcus gallinarum, which were prevalently detected in patients with PSC. A bacterial-organoid co-culture system visualized the epithelial-damaging effect of PSC-derived K. pneumoniae that was associated with bacterial translocation and susceptibility to T H 17-mediated hepatobiliary injuries. We also show that antibiotic treatment ameliorated the T H 17 immune response induced by PSC-derived microbiota. These results highlight the role of pathobionts in intestinal barrier dysfunction and liver inflammation, providing insights into therapeutic strategies for PSC.

  • A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

    Tanoue T., Morita S., Plichta D., Skelly A., Suda W., Sugiura Y., Narushima S., Vlamakis H., Motoo I., Sugita K., Shiota A., Takeshita K., Yasuma-Mitobe K., Riethmacher D., Kaisho T., Norman J., Mucida D., Suematsu M., Yaguchi T., Bucci V., Inoue T., Kawakami Y., Olle B., Roberts B., Hattori M., Xavier R., Atarashi K., Honda K.

    Nature (Nature)  565 ( 7741 ) 600 - 605 2019年01月

    ISSN  00280836

     概要を見る

    © 2019, Springer Nature Limited. There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103 + dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.

  • Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid

    Morita H., Kubo T., Rückert B., Ravindran A., Soyka M., Rinaldi A., Sugita K., Wawrzyniak M., Wawrzyniak P., Motomura K., Tamari M., Orimo K., Okada N., Arae K., Saito K., Altunbulakli C., Castro-Giner F., Tan G., Neumann A., Sudo K., O'Mahony L., Honda K., Nakae S., Saito H., Mjösberg J., Nilsson G., Matsumoto K., Akdis M., Akdis C.

    Journal of Allergy and Clinical Immunology (Journal of Allergy and Clinical Immunology)  2019年

    ISSN  00916749

     概要を見る

    © 2019 American Academy of Allergy, Asthma & Immunology Background: Group 2 innate lymphoid cells (ILC2s) play critical roles in induction and exacerbation of allergic airway inflammation. Thus clarification of the mechanisms that underlie regulation of ILC2 activation has received significant attention. Although innate lymphoid cells are divided into 3 major subsets that mirror helper effector T-cell subsets, counterpart subsets of regulatory T cells have not been well characterized. Objective: We sought to determine the factors that induce regulatory innate lymphoid cells (ILCregs). Methods: IL-10 + ILCregs induced from ILC2s by using retinoic acid (RA) were analyzed with RNA-sequencing and flow cytometry. ILCregs were evaluated in human nasal tissue from healthy subjects and patients with chronic rhinosinusitis with nasal polyps and lung tissue from house dust mite– or saline-treated mice. Results: RA induced IL-10 secretion by human ILC2s but not type 2 cytokines. IL-10 + ILCregs, which were converted from ILC2s by means of RA stimulation, expressed a regulatory T cell–like signature with expression of IL-10, cytotoxic T lymphocyte–associated protein 4, and CD25, with downregulated effector type 2–related markers, such as chemoattractant receptor–homologous molecule on T H 2 cells and ST2, and suppressed activation of CD4 + T cells and ILC2s. ILCregs were rarely detected in human nasal tissue from healthy subjects or lung tissue from saline-treated mice, but numbers were increased in nasal tissue from patients with chronic rhinosinusitis with nasal polyps and in lung tissue from house dust mite–treated mice. Enzymes for RA synthesis were upregulated in airway epithelial cells during type 2 inflammation in vivo and by IL-13 in vitro. Conclusion: We have identified a unique immune regulatory and anti-inflammatory pathway by which RA converts ILC2s to ILCregs. Interactions between airway epithelial cells and ILC2s play an important roles in the generation of ILCregs.

  • Mining the microbiota for microbial and metabolite-based immunotherapies

    Skelly A., Sato Y., Kearney S., Honda K.

    Nature Reviews Immunology (Nature Reviews Immunology)  2019年

    ISSN  14741733

     概要を見る

    © 2019, The Author(s), under exclusive licence to Springer Nature Limited. Trillions of microorganisms transit through and reside in the mammalian gastrointestinal tract each day, collectively producing thousands of small molecules and metabolites with local and systemic effects on host physiology. Identifying effector microorganisms that causally affect host phenotype and deciphering the underlying mechanisms have become foci of microbiome research and have begun to enable the development of microbiota-based therapeutics. Two complementary, reductionist approaches have commonly been used: the first starts with an immune phenotype and narrows down the microbiota to identify responsible effector bacteria, while the second starts with bacteria-derived molecules and metabolites and seeks to understand their effects on the host immune system. Together, these strategies provide the basis for the rational design of microbial and metabolite-based therapeutics that target and ameliorate immune deficits in patients.

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競争的資金等の研究課題 【 表示 / 非表示

  • 常在細菌叢の動作原理理解に基づく微生物製剤の開発

    2020年07月
    -
    2026年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 本田 賢也, 特別推進研究, 補助金,  代表

受賞 【 表示 / 非表示

  • Clarivate Analytics Highly Cited Researchers 2018

    2018年11月

    受賞区分: 学会誌・学術雑誌による顕彰

  • 第87回北里賞

    2018年06月, 慶應義塾大学医学部, 免疫系に深く影響を与える腸内細菌株の同定とその臨床応用に関する研究

    受賞区分: 塾内表彰等

  • Clarivate Analytics Highly Cited Researchers 2017

    2017年11月

    受賞区分: 学会誌・学術雑誌による顕彰

  • 第53回(2016年度)ベルツ賞

    2016年11月, 腸内細菌叢と宿主免疫相互作用インターフェースの理解と臨床応用

  • Clarivate Analytics Highly Cited Researchers 2016

    2016年11月

    受賞区分: 学会誌・学術雑誌による顕彰

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担当授業科目 【 表示 / 非表示

  • 微生物学・免疫学演習

    2021年度

  • 微生物学・免疫学実習

    2021年度

  • 微生物学・免疫学

    2021年度

  • 微生物学

    2021年度

  • 微生物学・免疫学特論

    2021年度

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担当経験のある授業科目 【 表示 / 非表示

  • 微生物学

    慶應義塾, 2015年度