研究・産学連携推進機構
学術支援センター
English
更新日：2025/01/23
准教授
ｼﾝﾅｶｽ　ﾘﾖｳ
新中須　亮
  • 1977年生まれ
  • Tel.089-960-5450

学位

  1. 博士（医学）千葉大学

研究分野

  1. ライフサイエンス免疫学液性免疫　感染症

研究キーワード

  1. 液性免疫　感染免疫

研究テーマ

  1. ウイルス感染症における液性免疫応答機序の解明2022/05/01-2027/03/31

共同・受託研究希望テーマ

  1. 微生物感染における生体防御機構
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共同研究・競争的資金等の研究課題

  1. 大阪大学変異インフルエンザウイルス感染防御に有効な記憶B細胞活性化機構の解明基盤研究(B)2021/04/01-2024/03/01
  2. 大阪大学インフルエンザウイルスに対する万能抗体誘導B細胞の誘導・維持機構の解明基盤研究(C)2017/04/01-2020/03/01
  3. 独立行政法人理化学研究所転写制御因子MeninによるB-1細胞の分化誘導・維持機構の解明若手研究(B)2014/04/01-2016/03/01
  4. 千葉大学アレルギー炎症における転写制御因子Gfi-1の役割解析若手研究(スタートアップ)
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論文

  1. Glycan engineering of the SARS-CoV-2 receptor-binding domain elicits cross-neutralizing antibodies for SARS-related viruses.2021/12/06Shinnakasu Ryo,Sakakibara Shuhei,Yamamoto Hiromi,Wang Po-Hung,Moriyama Saya,Sax Nicolas,Ono Chikako,Yamanaka Atsushi,Adachi Yu,Onodera Taishi,Sato Takashi,Shinkai Masaharu,Suzuki Ryosuke,Matsuura Yoshiharu,Hashii Noritaka,Takahashi Yoshimasa,Inoue Takeshi,Yamashita Kazuo,Kurosaki TomohiroThe Journal of experimental medicine218/ 1210.1084/jem.20211003Broadly protective vaccines against SARS-related coronaviruses that may cause future outbreaks are urgently needed. The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. These results have implications for the design of SARS-like virus vaccines.
  2. Identification of conserved SARS-CoV-2 spike epitopes that expand public cTfh clonotypes in mild COVID-19 patients.2021/12/06Lu Xiuyuan,Hosono Yuki,Nagae Masamichi,Ishizuka Shigenari,Ishikawa Eri,Motooka Daisuke,Ozaki Yuki,Sax Nicolas,Maeda Yuichi,Kato Yasuhiro,Morita Takayoshi,Shinnakasu Ryo,Inoue Takeshi,Onodera Taishi,Matsumura Takayuki,Shinkai Masaharu,Sato Takashi,Nakamura Shota,Mori Shunsuke,Kanda Teru,Nakayama Emi E,Shioda Tatsuo,Kurosaki Tomohiro,Takeda Kiyoshi,Kumanogoh Atsushi,Arase Hisashi,Nakagami Hironori,Yamashita Kazuo,Takahashi Yoshimasa,Yamasaki ShoThe Journal of experimental medicine218/ 1210.1084/jem.20211327Adaptive immunity is a fundamental component in controlling COVID-19. In this process, follicular helper T (Tfh) cells are a subset of CD4+ T cells that mediate the production of protective antibodies; however, the SARS-CoV-2 epitopes activating Tfh cells are not well characterized. Here, we identified and crystallized TCRs of public circulating Tfh (cTfh) clonotypes that are expanded in patients who have recovered from mild symptoms. These public clonotypes recognized the SARS-CoV-2 spike (S) epitopes conserved across emerging variants. The epitope of the most prevalent cTfh clonotype, S864-882, was presented by multiple HLAs and activated T cells in most healthy donors, suggesting that this S region is a universal T cell epitope useful for booster antigen. SARS-CoV-2-specific public cTfh clonotypes also cross-reacted with specific commensal bacteria. In this study, we identified conserved SARS-CoV-2 S epitopes that activate public cTfh clonotypes associated with mild symptoms.
  3. Exit from germinal center to become quiescent memory B cells depends on metabolic reprograming and provision of a survival signal.2021/01/04Inoue Takeshi,Shinnakasu Ryo,Kawai Chie,Ise Wataru,Kawakami Eiryo,Sax Nicolas,Oki Toshihiko,Kitamura Toshio,Yamashita Kazuo,Fukuyama Hidehiro,Kurosaki TomohiroThe Journal of experimental medicine218/ 110.1084/jem.20200866A still unanswered question is what drives the small fraction of activated germinal center (GC) B cells to become long-lived quiescent memory B cells. We found here that a small population of GC-derived CD38intBcl6hi/intEfnb1+ cells with lower mTORC1 activity favored the memory B cell fate. Constitutively high mTORC1 activity led to defects in formation of the CD38intBcl6hi/intEfnb1+ cells; conversely, decreasing mTORC1 activity resulted in relative enrichment of this memory-prone population over the recycling-prone one. Furthermore, the CD38intBcl6hi/intEfnb1+ cells had higher levels of Bcl2 and surface BCR that, in turn, contributed to their survival and development. We also found that downregulation of Bcl6 resulted in increased expression of both Bcl2 and BCR. Given the positive correlation between the strength of T cell help and mTORC1 activity, our data suggest a model in which weak help from T cells together with provision of an increased survival signal are key for GC B cells to adopt a memory B cell fate.
  4. Generation of High Quality Memory B Cells.2021Inoue Takeshi,Shinnakasu Ryo,Kurosaki TomohiroFrontiers in immunology12, 82581310.3389/fimmu.2021.825813Protection against pathogen re-infection is mediated, in large part, by two humoral cellular compartments, namely, long-lived plasma cells and memory B cells. Recent data have reinforced the importance of memory B cells, particularly in response to re-infection of different viral subtypes or in response with viral escape mutants. In regard to memory B cell generation, considerable advancements have been made in recent years in elucidating its basic mechanism, which seems to well explain why the memory B cells pool can deal with variant viruses. Despite such progress, efforts to develop vaccines that induce broadly protective memory B cells to fight against rapidly mutating pathogens such as influenza virus and HIV have not yet been successful. Here, we discuss recent advances regarding the key signals and factors regulating germinal center-derived memory B cell development and activation and highlight the challenges for successful vaccine development.
  5. Influenza vaccination strategies targeting the hemagglutinin stem region.2020/07Fukuyama Hidehiro,Shinnakasu Ryo,Kurosaki TomohiroImmunological reviews296/ 1, 132-14110.1111/imr.12887Influenza is one of the best examples of highly mutable viruses that are able to escape immune surveillance. Indeed, in response to influenza seasonal infection or vaccination, the majority of the induced antibodies are strain-specific. Current vaccine against the seasonal strains with the strategy of surveillance-prediction-vaccine does not cover an unmet virus strain leading to pandemic. Recently, antibodies targeting conserved epitopes on the hemagglutinin (HA) protein have been identified, albeit rarely, and they often showed broad protection. These antibody discoveries have brought the feasibility to develop a universal vaccine. Most of these antibodies bind the HA stem domain and accumulate in the memory B cell compartment. Broadly reactive stem-biased memory responses were induced by infection with antigenically divergent influenza strains and were able to eradicate these viruses, together indicating the importance of generating memory B cells expressing high-quality anti-stem antibodies. Here, we emphasize recent progress in our understanding of how such memory B cells can be generated and discuss how these advances may be relevant to the quest for a universal influenza vaccine.
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担当授業科目

  1. 2024医科学研究支援部門 講義・演習・実習
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