Graduate School of Medicine
医学専攻
日本語
Update date：2024/12/27
Senior Assistant Professor
Suzuki Junpei

Degree

  1. 博士(薬学)千葉大学大学院

Research Areas

Research Interests

  1. Immunology

Research Projects

  1. Investigation of the role of Menin in immunosenescense and cellular energy metabolism若手研究(B)Principal investigator
  2. The nuclear lamina regulates T-cell senescence via altering chromatin structure若手研究(B)Principal investigator
  3. Rabによるオートファジーを介したアレルギー性気道炎症の慢性化機序の解明基盤研究(C)Principal investigator
  4. 文部科学省科学研究費基盤研究(C)Rabによるオートファジーを介したアレルギー性気道炎症の慢性化機序の解明2019-2021Principal investigator
  5. Ehime UniversityThe nuclear lamina regulates T-cell senescence via altering chromatin structureGrant-in-Aid for Young Scientists (B)2017/04/01-2019/03/01
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Books and Other Publications

  1. T細胞老化のエピジェネティック制御 (第1土曜特集 免疫リプログラミングと細胞デザイン) -- (エピゲノムおよび転写制御による免疫リプログラミング)鈴木 淳平, 桑原 誠, 山下 政克医歯薬出版2020/10/030039-2359URL
  2. グルタミン代謝調節を介したT細胞老化制御鈴木 淳平, 桑原 誠, 山下 政克愛媛医学会2020/030286-3677
  3. 【代謝とがん免疫】グルタミン代謝によるCD8 T細胞抗腫瘍活性の調節鈴木 淳平, 名部 彰悟, 安川 正貴, 山下 政克(株)癌と化学療法社2020/010385-0684近年のがん治療では、T細胞養子免疫療法が一定の効果を上げ注目を集めている。T細胞養子免疫療法では、必ずT細胞をin vitroで培養後、患者の体内に戻す。しかしin vitroで培養したT細胞では、T細胞疲弊や細胞老化が誘導され、生体内で抗腫瘍活性を十分に発揮できないことがわかってきた。そのため、T細胞の抗腫瘍活性を最大限に発揮させるためにT細胞疲弊や老化を回避し、長期にわたり免疫応答を持続できるT細胞培養技術の開発が望まれている。最近の研究から、T細胞は活性化に伴い細胞内代謝状態を劇的に変化させることが明らかになってきた。これまでに筆者らは、T細胞の活性化に伴って誘導されるグルタミン代謝が過剰に活性化することで、T細胞疲弊や老化が誘導されることを見いだしている。そこで、グルタミン代謝の調節により抗腫瘍活性の高いCD8 T細胞を作製できると考え研究を行った。その結果、グルタミン制限培地で培養したCD8 T(dGln-CD8 T)細胞は通常状態で培養したCD8 T(Ctrl-CD8 T)細胞に比べ、移入後in vivoで強い抗腫瘍活性を示すことがわかった。dGln-CD8 T細胞では、腫瘍組織に浸潤する抗原特異的CD8 T細胞数の増加や細胞増殖能が維持されるだけでなく、T細胞疲弊マーカーであるPD-1の発現が低下していた。さらにdGln-CD8 T細胞は腫瘍特異的メモリーCD8 T細胞分化が亢進することもわかった。グルタミン制限の効果は、グルタミン代謝産物であるα-ケトグルタル酸で拮抗されたことから、抗腫瘍活性の調節におけるグルタミン代謝の重要性が示された。以上の結果から、グルタミン代謝を制限してT細胞を培養することでT細胞疲弊や老化を回避し、効率的にメモリーT細胞へ分化するCD8 T細胞の調製が可能となり、T細胞養子免疫療法の効果を増強できる可能性が示された。(著者抄録)
  4. 【免疫系を介したシステム連関:恒常性の維持と破綻】免疫細胞における代謝調節　T細胞老化・疲弊と細胞内エネルギー代謝鈴木 淳平, 山下 政克(公財)金原一郎記念医学医療振興財団2019/040370-9531＜文献概要＞リンパ球の一種であるT細胞の老化・疲弊は,加齢関連疾患の発症の大きなリスクファクターとなる。よって,T細胞老化・疲弊誘導の分子機構を理解することは,加齢関連疾患の発症予防や新規治療法の開発につながると考えられる。T細胞は,T細胞受容体(T cell receptor;TCR)を介し抗原を認識したのち,エフェクターT細胞へ機能分化する。その際,T細胞は細胞内の代謝状態を劇的に変化させることがわかってきている。代謝変化は老化・疲弊を含むT細胞の運命決定にかかわることが予想されるものの,その詳細な役割は不明である。そこで本稿では,筆者らの検討結果と最近の知見を中心にグルタミン代謝調節によるT細胞老化・疲弊誘導制御の可能性について述べる。
  5. T細胞老化・疲弊と細胞内エネルギー代謝 (特集 免疫系を介したシステム連関 : 恒常性の維持と破綻) -- (免疫細胞における代謝調節)鈴木 淳平, 山下 政克金原一郎記念医学医療振興財団 ; 1949-2019/030370-9531URL
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Papers

  1. Glucocorticoid imprints a low glucose metabolism onto CD8 T cells and induces the persistent suppression of the immune response.2021/12/17Amane Konishi, Junpei Suzuki, Makoto Kuwahara, Akira Matsumoto, Shunsuke Nomura, Tomoyoshi Soga, Toshihiro Yorozuya, Masakatsu YamashitaBiochemical and biophysical research communications588, 34-40Research paper (scientific journal)10.1016/j.bbrc.2021.12.050
  2. Glycolysis and subsequent mevalonate biosynthesis play an important role in Th2 cell differentiation.2020/09/17Yagi Yuichiro,Kuwahara Makoto,Suzuki Junpei,Imai Yasushi,Yamashita MasakatsuBiochemical and biophysical research communications530/ 2, 355-36110.1016/j.bbrc.2020.08.009Th2 cytokine such as IL-4, IL -5 and IL-13 are important therapeutic targets for Th2-type chronic inflammation. Several biologics targeting Th2 cytokine and its receptors are effective in clinical practice; however, the development of small-molecule compounds that inhibit Th2 cytokine productions is awaited. We found that an inhibitor for pyruvate dehydrogenase kinase (PDHK) suppresses the differentiation of IL-5/IL-13-producing Th2 cells. The expression of the Th2-related transcriptional factors Pparγ was decreased by treatment with inhibitor, whereas Gata3, a master regulator of Th2 cell differentiation, remained unchanged. The oxygen consumption rate was unaffected, whereas the level of farnesylated proteins was decreased by the PDHK inhibitor. Furthermore, the inhibitors for farnesyltransferase and hydroxymethylglutaryl-CoA reductase showed an inhibitory effect similar to that of the PDHK inhibitor. These results suggest that the mevalonate biosynthesis and subsequent protein prenylation may be novel therapeutic target for Th2 cell-dependent immune dysregulation, such as in allergic diseases.
  3. PEPPI-MS: Polyacrylamide-Gel-Based Prefractionation for Analysis of Intact Proteoforms and Protein Complexes by Mass Spectrometry.2020/07/11Ayako Takemori David S Butcher Victoria M Harman Philip Brownridge Keisuke Shima Daisuke Higo Jun Ishizaki Hitoshi Hasegawa Junpei Suzuki Masakatsu Yamashita Joseph A Loo Rachel R Ogorzalek Loo Robert J Beynon Lissa C Anderson Nobuaki TakemoriJournal of proteome researchResearch paper (scientific journal)10.1021/acs.jproteome.0c00303Prefractionation of complex mixtures of proteins derived from biological samples is indispensable for proteome analysis via top-down mass spectrometry (MS). Polyacrylamide gel electrophoresis (PAGE), which enables high-resolution protein separation based on molecular size, is a widely used technique in biochemical experiments and has the potential to be useful in sample fractionation for top-down MS analysis. However, the lack of a means to efficiently recover the separated proteins in-gel has always been a barrier to its use in sample prefractionation. In this study, we present a novel experimental workflow, called Passively Eluting Proteins from Polyacrylamide gels as Intact species for MS ("PEPPI-MS"), which allows top-down MS of PAGE-separated proteins. The optimization of Coomassie brilliant blue staining followed by the passive extraction step in the PEPPI-MS workflow enabled the efficient recovery of proteins, separated on commercial precast gels, from a wide range of molecular weight regions in under 10 min. Two-dimensional separation combining offline PEPPI-MS with online reversed-phase liquid chromatographic separation resulted in identification of over 1000 proteoforms recovered from the target region of the gel (≤50 kDa). Given the widespread availability and relatively low cost of traditional sodium dodecyl sulfate (SDS)-PAGE equipment, the PEPPI-MS workflow will be a powerful prefractionation strategy for top-down proteomics.
  4. [Glutamine Regulates the Antitumor Activity of CD8 T Cells].2020/01Suzuki Junpei,Nabe Shogo,Yasukawa Masaki,Yamashita MasakatsuGan to kagaku ryoho. Cancer & chemotherapy47/ 1, 11-15The cancer immunotherapies based on adoptive T cell therapy(ACT)has been receiving increased attention by improvement of the curative effect. T cells for ACT are harvested from the patient, then activated and expanded in vitro. However, in vitro activated T cells frequently show dysfunction after adoptive transfer, such as the exhaustion and the senescence. The exhausted/senescent T cells reduces the effector functions and fails to eliminate tumor cells. Therefore, the development of the culture method avoiding a T cellexhaustion and senescence. Recent findings revealthe dramatic changes of the metabolic status in T cells during T-cell receptor(TCR)-mediated activation. We recently reported that the activation status of glutaminolysis during TCR-stimulation determines the activated CD8 T cell fate. We considered that the therapeutic effect of ACT will be improved by the modulation of glutaminolysis. We demonstrated that the CD8 T cell exhaustion and/or senescence is prevented and the antitumor activity of adoptively transferred CD8 T cells is reinforced by the glutamine restriction during in vitro culture. The adoptively transferred CD8 T cells cultured under glutamine-restricted conditions shows higher infiltration in the tumor sites than that of CD8 T cells cultured under normal conditions. The expression of inhibitory receptors, such as PD-1 is decreased in tumor-infiltrating CD8 T cells cultured under glutamine-restricted conditions. Furthermore, the restriction of glutamine during CD8 T cell activation in vitro drives memory T cell development after adoptive transfer. The effect of glutamine restriction is antagonized by a-ketoglutarate, a metabolite of glutaminolysis. Thus, our recent findings suggest that the glutamine-restricted culture of CD8 T cells in vitro will improve the efficacy of CD8 T cell-based ACT.
  5. Pyrrothiogatain acts as an inhibitor of GATA family proteins and inhibits Th2 cell differentiation in vitro.2019/11Nomura S Takahashi H Suzuki J Kuwahara M Yamashita M Sawasaki TScientific reports9/ 1, 1733510.1038/s41598-019-53856-1
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Awards

  1. 2019/062018年日本抗加齢医学会研究助成奨励賞
  2. 2019/03平成30年度愛媛大学大学院医学系研究科長優秀論文賞・最優秀
  3. 2018/05第18回日本抗加齢医学会総会・優秀演題
  4. 2016/04平成28年度Tadamitsu Kishimoto International Travel Award
  5. 2016/02第44回日本免疫学会学術集会・ベストプレゼンテーション賞
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Allotted Class

  1. 2020Immunity
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Professional Memberships

  1. THE JAPANESE SOCIETY FOR IMMUNOLOGY
  2. 日本抗加齢医学会
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