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Affiliation |
Graduate School of Medicine Doctorial Course in Medicine Bioregulatory Medicine Department of Medical Biology |
TATEMATU Megumi
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Graduating School 【 display / non-display 】
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-2008.03
Hokkaido University Faculty of Pharmaceutical Science Graduated
Graduate School 【 display / non-display 】
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-2013.09
Hokkaido University Graduate School,Division of Medicine Doctor's Course Completed
Campus Career 【 display / non-display 】
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2020.08-Now
Akita University Graduate School of Medicine Doctorial Course in Medicine Bioregulatory Medicine Assistant Professor
Research Areas 【 display / non-display 】
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Life Science / Pathological biochemistry
Research Achievements 【 display / non-display 】
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TIGIT mediates activation-induced cell death of ILC2s during chronic airway allergy.
Toshiki Yamada, Megumi Tatematsu, Shunsuke Takasuga, Akane Fuchimukai, Kenki Yamagata, Shinsuke Seki, Keiji Kuba, Hideyuki Yoshida, Ichiro Taniuchi, Günter Bernhardt, Kazuko Shibuya, Akira Shibuya, Takechiyo Yamada, Takashi Ebihara
The Journal of experimental medicine 220 ( 7 ) 2023.07
Research paper (journal)
While group-2 innate lymphoid cells (ILC2s) are highly proliferative in allergic inflammation, the removal of overactivated ILC2s in allergic diseases has not been investigated. We previously showed that chronic airway allergy induces "exhausted-like" dysfunctional ILC2s expressing T cell immunoreceptor with Ig and ITIM domains (TIGIT). However, the physiological relevance of these cells in chronic allergy remains elusive. To precisely identify and monitor TIGIT+ ILC2s, we generated TIGIT lineage tracer mice. Chronic allergy stably induced TIGIT+ ILC2s, which were highly activated, apoptotic, and were quickly removed from sites of chronic allergy. Transcripts from coding genes were globally suppressed in the cells, possibly due to reduced chromatin accessibility. Cell death in TIGIT+ ILC2s was enhanced by interactions with CD155 expressed on macrophages, whereas genetic ablation of Tigit or blockade by anti-TIGIT antagonistic antibodies promoted ILC2 survival, thereby deteriorating chronic allergic inflammation. Our work demonstrates that TIGIT shifts the fate of ILC2s toward activation-induced cell death, which could present a new therapeutic target for chronic allergies.
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Trained innate lymphoid cells in allergic diseases
Ebihara T, Tatematsu M, Fuchimukai A, Yamada T, Yamagata K, Takasuga S, Yamada T
Allergology International 2020.12 [Refereed] [Invited]
Research paper (journal) Domestic Co-author
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Toward Establishing an Ideal Adjuvant for Non-Inflammatory Immune Enhancement.
Tsukasa Seya, Megumi Tatematsu, Misako Matsumoto
Cells 11 ( 24 ) 2022.12
The vertebrate immune system functions to eliminate invading foreign nucleic acids and foreign proteins from infectious diseases and malignant tumors. Because pathogens and cancer cells have unique amino acid sequences and motifs (e.g., microbe-associated molecular patterns, MAMPs) that are recognized as "non-self" to the host, immune enhancement is one strategy to eliminate invading cells. MAMPs contain nucleic acids specific or characteristic of the microbe and are potential candidates for immunostimulants or adjuvants. Adjuvants are included in many vaccines and are a way to boost immunity by deliberately administering them along with antigens. Although adjuvants are an important component of vaccines, it is difficult to evaluate their efficacy ex vivo and in vivo on their own (without antigens). In addition, inflammation induced by currently candidate adjuvants may cause adverse events, which is a hurdle to their approval as drugs. In addition, the lack of guidelines for evaluating the safety and efficacy of adjuvants in drug discovery research also makes regulatory approval difficult. Viral double-stranded (ds) RNA mimics have been reported as potent adjuvants, but the safety barrier remains unresolved. Here we present ARNAX, a noninflammatory nucleic acid adjuvant that selectively targets Toll-like receptor 3 (TLR3) in antigen-presenting dendritic cells (APCs) to safely induce antigen cross-presentation and subsequently induce an acquired immune response independent of inflammation. This review discusses the challenges faced in the clinical development of novel adjuvants.
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Human genetic defects in SRP19 and SRPRA cause severe congenital neutropenia with distinctive proteome changes.
Monika I Linder, Yoko Mizoguchi, Sebastian Hesse, Gergely Csaba, Megumi Tatematsu, Marcin Łyszkiewicz, Natalia Zietara, Tim Jeske, Maximilian Hastreiter, Meino Rohlfs, Yanshan Liu, Piotr Grabowski, Kaarin Ahomaa, Daniela Maier-Begandt, Marko Schwestka, Vahid Pazhakh, Abdulsalam Isiaku, Brenda Briones Miranda, Piers Blombery, Megumu K Saito, Ejona Rusha, Zahra Alizadeh, Zahra Pourpak, Masao Kobayashi, Nima Rezaei, Ekrem Unal, Fabian Hauck, Micha Drukker, Barbara Walzog, Juri Rappsilber, Ralf Zimmer, Graham J Lieschke, Christoph Klein
Blood 2022.10
The mechanisms of coordinated changes in proteome composition and their relevance for the differentiation of neutrophil granulocytes are not well studied. Here, we discover two novel human genetic defects in SRPRA and SRP19, constituents of the mammalian co-translational targeting machinery and characterize their role in neutrophil granulocyte differentiation. We systematically study the proteome of neutrophil granulocytes from patients with variants in the signal recognition particle (SRP) genes, HAX1, and ELANE and identify global as well as specific proteome aberrations. Using in vitro differentiation of human induced pluripotent stem cells and in vivo zebrafish models, we study the effects of SRP-deficiency on neutrophil granulocyte development. In a heterologous cell-based inducible protein expression system, we validate the effects conferred by SRP dysfunction for selected proteins that we identified in our proteome screen. Thus, SRP-dependent protein processing, intracellular trafficking and homeostasis are critically important for the differentiation of neutrophil granulocytes.
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Ccr4-NOT脱アデニル化酵素複合体は抗腫瘍性NK細胞活性を制御する(The Ccr4-Not deadenylase complex controls antitumor NK cell activity)
Tatematsu Megumi, Sawa Shinichiro, Ikuta Koichi, Ebihara Takashi
日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 ) 50 ( Proceedings ) 3 - P 2021.11
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ILC2の活性化により生じる細胞死は慢性アレルギー性炎症に対し保護的に働く(Activation-induced cell death of ILC2s confersprotection against chronic allergic inflammation)
Yamada Toshiki, Tatematsu Megumi, Ebihara Takashi
日本免疫学会総会・学術集会記録 ( (NPO)日本免疫学会 ) 50 ( Proceedings ) 3 - P 2021.11
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Defects in Signal Recognition Particle (SRP) Components Reveal an Essential and Non-Redundant Role for Granule Biogenesis and Differentiation of Neutrophil Granulocytes
Yoko Mizoguchi, Sebastian Hesse, Monika Linder, Natalia Zietara, Marcin Lyszkiewicz, Yanshan Liu, Megumi Tatematsu, Piotr Grabowski, Kaarin Ahomaa, Tim Jeske, Sebastian Hollizeck, Ejona Rusha, Megumu K. Saito, Masao Kobayashi, Zahra Alizadeh, Zahra Pourpak, Sorin Iurian, Nima Rezaei, Ekrem Unal, Micha Drukker, Barbara Walzog, Fabian Hauck, Juri Rappsilber, Christoph Klein
BLOOD ( AMER SOC HEMATOLOGY ) 134 2019.11
Summary of the papers read (international conference)
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◆Original paper【 display / non-display 】
◆Other【 display / non-display 】
Grant-in-Aid for Scientific Research 【 display / non-display 】
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Grant-in-Aid for JSPS Fellows
Project Year： 2018.10 - 2020.07
Presentations 【 display / non-display 】
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Cnot3 differentially regulates development and function of innate lymphoid cells
Megumi Tatematsu, Akane Fuchimukai, Shunsuke Takasuga, Toshiki Yamada, Kenji Ishiwata, Ichiro Taniuchi, Shinichiro Sawa, Keiji Kuba, Takashi Ebihara
第52回日本免疫学会学術集会 2024.01 - 2024.01
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Caloric restriction induces cellular quiescence in hepatic ILC1s
Tatematsu M, Fuchimukai A, Nabekura T, Shibuya A, and Ebihara T
第51回日本免疫学会学術集会 2022.12 - 2022.12
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The Ccr4-Not deadenylase complex controls antitumor NK cell activity
Megumi Tatematsu, Shinichiro Sawa, Koichi Ikuta, Takashi Ebihara
The 50th Annual Meeting of the Japanese Society for Immunology (奈良) 2021.12 - 2021.12 日本免疫学会
NK cells are critical cytotoxic lymphocytesmediating antitumor immune responses. NK cell activity is regulated by posttranslationalmechanisms including mRNA processing, splicing, modification, polyadenylation, andstability. Many miRNAs have been found to modulate NK cell development,maturation, survival, and function by degradation of the target mRNAs. However,mRNA degradation is mainly controlled by poly A deadenylation mediated by the Ccr4-Notdeadenylase complex in mammals. To clarify physiological impact of mRNAstability itself in Group I innate lymphoid cells including NK cells, wedeleted Cnot3, a major functional component of the Ccr4-Not deadenylasecomplex, in ILCs. Absence of Cnot3 led to no differentiation of liver ILC1s andthe reduction in number of splenic NK cells, but almost normal differentiationof ILC1s in the intestine. Cnot3-deficient NK cells exhibited immaturephenotype accompanied by low IFNg responses and low degranulation capability.Furthermore, Cnot3 was required for NK cells to suppress B16F10 tumormetastasis in the lung. We are currently examining how Cnot3 shapes homeostasisof Group I innate lymphoid cells in tissues and regulates antitumor activity ofNK cells.
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TLR 3 recognizes single-stranded RNA with incomplete stem structures
Nishikawa F, Seya T, Matsumoto M
第15回国際免疫学会 (ミラノ) 2013.08 - 2013.08
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Virus-derived single-stranded RNA with stable secondary structure extracellularly activates Toll-like receptor 3
Seya T, Matsumoto M
IUMS2011 (札幌) 2011.09 - 2011.09