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大学院医学系研究科（医学専攻等） 医学専攻 病態制御医学系 微生物学講座 |
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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年07月
研究論文（学術雑誌）
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年12月 [査読有り] [招待有り]
研究論文（学術雑誌） 国内共著
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Toward Establishing an Ideal Adjuvant for Non-Inflammatory Immune Enhancement.
Tsukasa Seya, Megumi Tatematsu, Misako Matsumoto
Cells 11 ( 24 ) 2022年12月
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年10月
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年11月
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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年11月
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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年11月
研究発表要旨（国際会議）
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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年01月 - 2024年01月
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Ccr4-not複合体による自然リンパ球の制御
立松恵、高須賀俊輔、渕向茜、海老原敬
第75回日本細菌学会東北支部学術集会 2023年08月 - 2023年08月
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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年12月 - 2022年12月
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ACTIVATION-INDUCED CELL DEATH OF ILC2 REGULATES CHRONIC ALLERGIC INFLAMMATION
Yamada T, Tatematsu M, Takasuga S, Yamagata K, Shibuya K, Shibuya A, Yamada T, Ebihara T
4th International Conference on Innate Lymphoid Cells 2022年09月 - 2022年09月
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低栄養状態により誘導されるILC1 Quiescence
立松恵, 渕向茜, 海老原敬
第７４回日本細菌学会東北支部会 学術集会・総会 2022年08月 - 2022年08月