Updated on 2025/12/14

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写真a

 
Hiroyuki Yagyu
 
Organization
Yokohama City University Hospital Assistant Professor
Title
Assistant Professor
External link

Research Interests

  • Asthma

  • T cells

  • Allergy

  • Interstitial lung disease

  • 免疫代謝

Research Areas

  • Life Science / Immunology

  • Life Science / Respiratory medicine

Professional Memberships

Papers

  • Hepatic leukemia factor directs tissue residency of proinflammatory memory CD4 + T cells

    Masahiro Kiuchi, Masahiro Nemoto, Hiroyuki Yagyu, Ami Aoki, Chiaki Iwamura, Hikaru Sugimoto, Yuki Masuo, Hajime Morita, Shuhe Ma, Yukiko Okuno, Takahisa Hishiya, Kaori Tsuji, Atsushi Sasaki, Kota Kokubo, Kanae Ohishi, Rie Shinmi, Yuri Sonobe, Tomohisa Iinuma, Syuji Yonekura, Tomomasa Yokomizo, Norio Komatsu, Atsushi Onodera, Shinya Okumura, Takashi Ito, Etsuro Hatano, Tatsuaki Tsuruyama, Yosuke Kurashima, Naoko Mato, Takuji Suzuki, Motoko Yagi Kimura, Shinichiro Motohashi, Eiryo Kawakami, Hideki Ueno, Damon J Tumes, Toyoyuki Hanazawa, Toshinori Nakayama, Kiyoshi Hirahara

    Science   2025.12

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    Publishing type：Research paper (scientific journal)  

    DOI： 10.1126/science.adp0714

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  • Lipolysis-microlipophagy cascade regulated by adipose triglyceride lipase drives pathogenic adaptive type 2 immunity

    Hiroyuki Yagyu, Masahiro Kiuchi, Atsushi Sasaki, Eisuke Itakura, Kota Kokubo, Chiaki Iwamura, Atsushi Onodera, Ami Aoki, Takahisa Hishiya, Kaori Tsuji, Takuto Hiramoto, Rie Shinmi, Yuri Sonobe, Takahiro Arano, Kanae Ohishi, Shigenori Baba, Junya Kurita, Tomohisa Iinuma, Syuji Yonekura, Yu Hara, Motoko Y. Kimura, Shinichiro Motohashi, Damon J. Tumes, Toyoyuki Hanazawa, Takeshi Kaneko, Toshinori Nakayama, Kiyoshi Hirahara

    Science Immunology   2025.10

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    Publishing type：Research paper (scientific journal)  

    DOI： 10.1126/sciimmunol.adp0849

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  • Valid surrogate end-points in nonsmall cell lung cancer peri-operative systemic therapy trials: a systematic review. International journal

    Kohei Somekawa, Nobuyuki Horita, Satoshi Nagaoka, Yukihito Kajita, Suguru Muraoka, Ami Izawa, Yukiko Otsu, Ayami Kaneko, Momo Hirata, Rei Inoue, Sousuke Kubo, Katsushi Tanaka, Ryo Nagasawa, Hiroyuki Yagyu, Kota Murohashi, Ayako Aoki, Yohei Kameda, Hiroaki Fujii, Keisuke Watanabe, Yu Hara, Hiroyuki Adachi, Nobuaki Kobayashi, Aya Saito, Takeshi Kaneko

    European respiratory review : an official journal of the European Respiratory Society   34 ( 178 )   2025.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: Recurrence-, progression-, disease- and event-free survival are often selected as the primary end-points for trials assessing peri-operative systemic therapy for nonsmall cell lung cancer (NSCLC). As overall survival (OS) has increased, these surrogates, which we hereafter collectively term "recurrence-/progression-free survivals (RPFS)", have become more attractive end-points. METHODS: This systematic review, without meta-analysis, was conducted in accordance with the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (UMIN000052558). Electronic databases were searched on 11 October 2023. English-language articles presenting a randomised controlled trial assessing neoadjuvant and/or adjuvant systemic therapy for NSCLC were included. The main outcome was the weighted Spearman's rank correlation coefficient (r) between the hazard ratios (HRs) of OS (HRos) and RPFS (HRrpfs). The weight assigned to each study was determined using the inverse variance of the log HRos. Pathological subtype and driver mutations were not questioned. RESULTS: We identified 31 trials with a total of 15 776 patients. The weighted correlation coefficient was 0.86 based on the raw data from the 31 trials. After reciprocal duplication, the weighted correlation coefficient was 0.91 (p<0.001 for unweighted r). Subgroup analyses showed the correlation was 0.98 for trials with immune checkpoint inhibitors but was 0.54 for molecular targeted therapy CONCLUSIONS: We hope that our data will justify the use of the HRs of recurrence-, progression-, disease- and event-free survival as primary end-points in peri-operative immune checkpoint inhibitor regimens for NSCLC.

    DOI： 10.1183/16000617.0034-2025

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  • [Clinical Management of Respiratory Diseases in Neurosurgical Settings].

    Hiroyuki Yagyu, Yu Hara, Takeshi Kaneko

    No shinkei geka. Neurological surgery   52 ( 6 )   1224 - 1233   2024.11

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    Language：Japanese   Publishing type：Research paper (scientific journal)  

    Respiratory diseases, such as chronic obstructive pulmonary disease(COPD)and asthma, are becoming increasingly prevalent in super-aging societies. In Japan, the estimated prevalence of COPD among individuals aged 40 years and above is 8.6%, while asthma affects about 10% of adults. These statistics highlight the similarities between COPD and asthma in clinical settings. Both diseases involve chronic airway inflammation and present with symptoms such as chronic cough, sputum production, wheezing, and dyspnea. Exacerbations of these symptoms and complications are critical concerns during the perioperative period. COPD, often caused by long-term smoking, leads to irreversible airway and lung damage, while asthma is characterized by episodic and reversible airway constriction due to chronic inflammation. COPD diagnosis involves spirometry and the exclusion of other diseases, with treatment goals focusing on symptom improvement and risk reduction through smoking cessation, pharmacotherapy(mainly bronchodilators), and non-pharmacological methods(such as pulmonary rehabilitation). Asthma management aims to control inflammation and prevent exacerbations using inhaled corticosteroids and bronchodilators as standard treatments. Perioperative management of both diseases involves improving respiratory function with pharmacotherapy, careful anesthesia selection, and early postoperative mobilization. Consultation with respiratory specialists is recommended for effective management, especially in complex cases.

    DOI： 10.11477/mf.1436205039

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  • The USP7-STAT3-granzyme-Par-1 axis regulates allergic inflammation by promoting differentiation of IL-5-producing Th2 cells. International journal

    Jin Kumagai, Masahiro Kiuchi, Kota Kokubo, Hiroyuki Yagyu, Masahiro Nemoto, Kaori Tsuji, Ken Nagahata, Atsushi Sasaki, Takahisa Hishiya, Miki Onoue, Rie Shinmi, Yuri Sonobe, Tomohisa Iinuma, Syuji Yonekura, Jun Shinga, Toyoyuki Hanazawa, Haruhiko Koseki, Toshinori Nakayama, Koutaro Yokote, Kiyoshi Hirahara

    Proceedings of the National Academy of Sciences of the United States of America   120 ( 49 )   e2302903120   2023.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    Uncontrolled type 2 immunity by type 2 helper T (Th2) cells causes intractable allergic diseases; however, whether the interaction of CD4+ T cells shapes the pathophysiology of allergic diseases remains unclear. We identified a subset of Th2 cells that produced the serine proteases granzyme A and B early in differentiation. Granzymes cleave protease-activated receptor (Par)-1 and induce phosphorylation of p38 mitogen-activated protein kinase (MAPK), resulting in the enhanced production of IL-5 and IL-13 in both mouse and human Th2 cells. Ubiquitin-specific protease 7 (USP7) regulates IL-4-induced phosphorylation of STAT3, resulting in granzyme production during Th2 cell differentiation. Genetic deletion of Usp7 or Gzma and pharmacological blockade of granzyme B ameliorated allergic airway inflammation. Furthermore, PAR-1+ and granzyme+ Th2 cells were colocalized in nasal polyps from patients with eosinophilic chronic rhinosinusitis. Thus, the USP7-STAT3-granzymes-Par-1 pathway is a potential therapeutic target for intractable allergic diseases.

    DOI： 10.1073/pnas.2302903120

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  • Single-cell immunoprofiling after immunotherapy for allergic rhinitis reveals functional suppression of pathogenic TH2 cells and clonal conversion. International journal

    Tomohisa Iinuma, Masahiro Kiuchi, Kiyoshi Hirahara, Junya Kurita, Kota Kokubo, Hiroyuki Yagyu, Riyo Yoneda, Tomoyuki Arai, Yuri Sonobe, Masaki Fukuyo, Atsushi Kaneda, Syuji Yonekura, Toshinori Nakayama, Yoshitaka Okamoto, Toyoyuki Hanazawa

    The Journal of allergy and clinical immunology   150 ( 4 )   850 - 860   2022.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: Allergic rhinitis is a growing problem worldwide. Currently the only treatment that can modify the disease is antigen-specific immunotherapy, but its mechanism of action is not fully understood. OBJECTIVE: We comprehensively investigated the role and changes of antigen-specific T cells before and after sublingual immunotherapy (SLIT) for Japanese cedar pollinosis. METHODS: We cultured peripheral blood mononuclear cells obtained both before and 1 year after initiating SLIT and used a combination of single-cell RNA sequencing and repertoire sequencing. To investigate biomarkers, we used cells from patients participating a phase 2/3 trial of SLIT tablets for Japanese cedar pollinosis and cells from outpatients with good and poor response. RESULTS: Antigen-stimulated culturing after SLIT led to clonal expansion of TH2 and regulatory T cells, and most of these CD4+ T cells retained their CDR3 regions before and after treatment, indicating antigen-specific clonal responses and differentiation resulting from SLIT. However, SLIT reduced the number of clonal functional TH2 cells but increased the trans-type TH2 cell population that expresses musculin (MSC), TGF-β, and IL-2. Trajectory analysis suggested that SLIT induced clonal differentiation of the trans-type TH2 cells differentiated into regulatory T cells. Using real-time PCR, we found that the MSC levels increased in the active SLIT group and those with good response after 1 year of treatment. CONCLUSION: The combination of single-cell RNA sequencing and repertoire analysis helped reveal part of the underlying mechanism: SLIT promotes the expression of MSC on pathogenic TH2 cells and suppresses their function. MSC may be a potential biomarker of SLIT for allergic rhinitis.

    DOI： 10.1016/j.jaci.2022.06.024

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  • Clinical utility of a composite scoring system including Charlson Comorbidity Index score in patients with interstitial lung disease. International journal

    Hiroyuki Yagyu, Kota Murohashi, Yu Hara, Yusuke Saigusa, Ayako Aoki, Nobuaki Kobayashi, Takeshi Kaneko

    Journal of thoracic disease   12 ( 10 )   5774 - 5782   2020.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: Prognostic factors have yet to be established for patients with interstitial lung disease (ILD). We aimed to clarify whether the Charlson Comorbidity Index score (CCIS) could help predict disease prognosis in patients with ILD. METHODS: Among ILD patients treated between April 2013 and April 2017, we retrospectively assessed the relationship between baseline clinical parameters including age, sex, CCIS, ILD diagnosis, pulmonary function test results, and 3-year ILD-related events including cause-specific death and first acute exacerbation (AE). RESULTS: We assessed 180 patients (mean age, 74 years), all of whom underwent pulmonary function testing including percentage predicted diffusion capacity for carbon monoxide (%DLco). Underlying pathologies included idiopathic pulmonary fibrosis (IPF) in 57 cases, idiopathic nonspecific interstitial pneumonia (iNSIP) and collagen vascular disease-related interstitial pneumonia in 117 cases, and chronic hypersensitivity pneumonia (CHP) in 6 cases. A composite scoring system comprising IPF diagnosis, CCIS, and %DLco provided a favorable C-index (0.825) for predicting 3-year ILD-related events. The nomogram for 3-year prognosis revealed the largest contributions from CCIS, %DLco and IPF diagnosis. CONCLUSIONS: This composite scoring system accounting for IPF diagnosis, CCIS, and %DLco could provide a useful tool for predicting prognosis in relatively mild ILD patients tolerated to pulmonary diffusion capacity testing.

    DOI： 10.21037/jtd-20-1302

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  • Serum surfactant protein A as a surrogate biomarker of a negative heart sign among patients with interstitial lung disease.

    Hisashi Sasaki, Yu Hara, Masataka Taguri, Yuji Fujikura, Kota Murohashi, Hiroyuki Yagyu, Takeshi Kaneko, Akihiko Kawana

    Nagoya journal of medical science   82 ( 3 )   499 - 508   2020.8

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    The mechanisms underlying interstitial lung disease (ILD) are characterized by variable inflammation or fibrosis of the pulmonary interstitium. A negative heart sign (NHS) on 67Ga scintigrams of patients with ILD is due to considerably increased inflammatory activity in the lungs. We retrospectively analyzed relationships between NHS and established biomarkers of disease severity in patients with ILD. Among 81 consecutive non-smoking patients with ILD (mean age, 63 years) who had been hospitalized between April 2009 and October 2011, we selected 52 who had been assessed by 67Ga scintigraphy. We then evaluated relationships between NHS and blood biomarkers, pulmonary function and high-resolution computed tomography (HRCT). Among these 52 patients, 10 showed idiopathic pulmonary fibrosis and 42 had other ILD. Multivariate analysis with stepwise variable selection, serum surfactant protein (SP)-A (OR (odds ratio), 1.026; 95%CI (confidence interval), 1.003-1.050; P = 0.024) and inflammation index calculated from HRCT findings (OR, 1.358; 95%CI, 1.079-1.709; P = 0.009) were significant predictors of an NHS. Serum SP-A offered 85% sensitivity and 75% specificity for predicting NHS at an optimal cut-off of 45.8 ng/mL. Serum SP-A concentrations correlated positively with inflammation index (r = 0.344, P = 0.015). In conclusion, serum SP-A might serve as a surrogate biomarker for predicting an NHS in patients with ILD.

    DOI： 10.18999/nagjms.82.3.499

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  • Giant Solitary Fibrous Tumor of Pleura Presenting Both Benign and Malignant Features. International journal

    Hiroyuki Yagyu, Yu Hara, Kota Murohashi, Yoshihiro Ishikawa, Tetsuya Isaka, Tetsukan Woo, Takeshi Kaneko

    The American journal of case reports   20   1755 - 1759   2019.11

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    BACKGROUND The incidence of solitary fibrous tumor of the pleura (SFTP) is less than 5% of all pleural tumors. It is important to determine whether the tumor is benign or malignant in deciding on treatment and estimating prognosis, but this can sometimes be difficult. CASE REPORT A 59-year-old woman with no prior medical history presented with a 4-month history of right back pain and dyspnea. Contrast-enhanced computed tomography revealed a giant oval mass with inhomogeneous intensities, and bloody pleural effusion in the right thoracic cavity, proved to be solitary fibrous tumor of pleura (SFTP) under the complete thoracoscopic resection. The resected tumor seemed to have several malignant features, including large size of tumor, inhomogeneous intensities, and pleural effusion due to intratumor hemorrhage; however, Ki-67 (MIB-I) proliferation index was less than 1%, with no recurrence seen within 2 year after symptom onset. CONCLUSIONS We managed a case of SFTP presenting both malignant and benign features. In patients with SFTP, multi-disciplinary discussion among the clinician, radiologist, and pathologist was considered to be needed for estimating disease prognosis.

    DOI： 10.12659/AJCR.919639

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