2022/09/29 更新

写真a

シマ ケンジロウ
島 賢治郎
SHIMA Kenjiro
所属
医歯学総合病院 呼吸器・感染症内科 助教
職名
助教
外部リンク

学位

  • 博士(医学) ( 2015年3月   新潟大学 )

研究分野

  • ライフサイエンス / 呼吸器内科学

経歴

  • 新潟大学   医歯学総合病院 呼吸器・感染症内科   助教

    2022年7月 - 現在

  • 新潟大学   医歯学総合病院 呼吸器・感染症内科   特任助教

    2021年4月 - 2022年6月

  • 新潟大学   医歯学総合病院 高度医療開発センター   特任助教

    2020年4月 - 2021年3月

 

論文

  • A Case Report of Occupational Lung Disease Caused by Exposure to Polytetrafluoroethylene.

    Ami Aoki, Akira Saito, Kenjiro Shima, Yosuke Kimura, Katsuaki Asakawa, Riuko Ohashi, Hajime Umezu, Takuro Sakagami, Hiroshi Moriyama, Toshiaki Kikuchi

    Internal medicine (Tokyo, Japan)   2022年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We herein report a 45-year-old-man with multiple foreign body granulomas in the lungs caused by polytetrafluoroethylene (PTFE). A mass in the right lower lobe of the lung and bilateral centrilobular lung nodules were found unexpectedly during the patient's visit to a hospital for a respiratory infection. The patient's occupation for 26 years involved spraying PTFE. A lung biopsy using bronchoscopy revealed granulomatous lesions and giant cells. The presence of fluorine in the granulomatous lesions was confirmed using an electron probe microanalyzer with wavelength dispersive spectrometer. Fluorine is a component of PTFE and is not found in normal lung tissue.

    DOI: 10.2169/internalmedicine.9008-21

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  • Two cases of dupilumab-associated eosinophilic pneumonia in asthma with eosinophilic chronic rhinosinusitis: IL-5-driven pathology? 国際誌

    Yuki Nishiyama, Toshiyuki Koya, Kei Nagano, Seitaro Abe, Yosuke Kimura, Kenjiro Shima, Mio Toyama-Kosaka, Takashi Hasegawa, Takanobu Sasaki, Kaori Shinbori, Shigeharu Ueki, Kaori Takamura, Toshiaki Kikuchi

    Allergology international : official journal of the Japanese Society of Allergology   2022年4月

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  • A Murine Model of Hereditary Pulmonary Alveolar Proteinosis Caused by Homozygous Csf2ra Gene Disruption. 国際誌

    Kenjiro Shima, Paritha Arumugam, Anthony Sallese, Yuko Horia, Yan Ma, Cole Trapnell, Matthew Wessendarp, Claudia Chalk, Cormac McCarthy, Brenna C Carey, Bruce C Trapnell, Takuji Suzuki

    American journal of physiology. Lung cellular and molecular physiology   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hereditary pulmonary alveolar proteinosis (hPAP) is a rare disorder caused by recessive mutations in GM-CSF receptor subunit a/b genes (CSF2RA/CSF2RB, respectively) characterized by impaired GM-CSF dependent surfactant clearance by alveolar macrophages (AMs) resulting in alveolar surfactant accumulation and hypoxemic respiratory failure. Because hPAP is caused by CSF2RA mutations in most patients, we created an animal model of hPAP caused by Csf2ra gene disruption (Csf2ra-/- mice) and evaluated the effects on AMs and lungs. Macrophages from Csf2ra-/- mice were unable to bind and clear GM-CSF, did not exhibit GM-CSF signaling, and had functional defects in phagocytosis, cholesterol clearance, and surfactant clearance. Csf2ra-/- mice developed a time-dependent, progressive lung disease similar to hPAP in children caused by CSF2RA mutations with respect to the clinical, physiological, histopathological, biochemical abnormalities, biomarkers of PAP lung disease, and clinical course. In contrast, Csf2ra+/- mice had functionally normal AMs and no lung disease. Pulmonary macrophage transplantation (PMT) without myeloablation resulted in long-term engraftment, restoration of GM-CSF responsiveness to AMs, and a safe and durable treatment effect that lasted for the duration of the experiment (6 months). Results show that homozygous (but not heterozygous) Csf2ra gene ablation caused hPAP identical to that in children with CSF2RA mutations, identified AMs as the cellular site of hPAP pathogenesis in Csf2ra-/- mice, and have implications for preclinical studies supporting the translation of PMT as therapy of hPAP in humans.

    DOI: 10.1152/ajplung.00175.2021

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  • 生物学的製剤・気管支熱形成術 Benralizumab導入前後での気道壁肥厚および気道閉塞の検討

    坪川 史人, 小屋 俊之, 田中 健太郎, 木村 陽介, 島 賢治郎, 外山 美央, 林 正周, 長谷川 隆志, 菊地 利明

    アレルギー   70 ( 6-7 )   791 - 791   2021年8月

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    記述言語:日本語   出版者・発行元:(一社)日本アレルギー学会  

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  • Effective hematopoietic stem cell-based gene therapy in a murine model of hereditary pulmonary alveolar proteinosis 査読 国際誌

    Miriam Hetzel, Elena Lopez-Rodriguez, Adele Mucci, Ariane Hai Ha Nguyen, Takuji Suzuki, Kenjiro Shima, Theresa Buchegger, Sabine Dettmer, Thomas Rodt, Jens P. Bankstahl, Punam Malik, Lars Knudsen, Axel Schambach, Gesine Hansen, Bruce C. Trapnell, Nico Lachmann, Thomas Moritz

    Haematologica   105 ( 4 )   1147 - 1157   2020年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Ferrata Storti Foundation (Haematologica)  

    Hereditary pulmonary alveolar proteinosis due to GM-CSF receptor deficiency (herPAP) constitutes a life-threatening lung disease characterized by alveolar deposition of surfactant protein secondary to defective alveolar macrophage function. As current therapeutic options are primarily symptomatic, we have explored the potential of hematopoietic stem cell-based gene therapy. Using Csf2rb-/- mice, a model closely reflecting the human herPAP disease phenotype, we here demonstrate robust pulmonary engraftment of an alveolar macrophage population following intravenous transplantation of lentivirally corrected hematopoietic stem and progenitor cells. Engraftment was associated with marked improvement of critical herPAP disease parameters, including bronchoalveolar fluid protein, cholesterol and cytokine levels, pulmonary density on computed tomography scans, pulmonary deposition of Periodic Acid-Schiff+ material as well as respiratory mechanics. These effects were stable for at least nine months. With respect to engraftment and alveolar macrophage differentiation kinetics, we demonstrate the rapid development of CD11c+/SiglecF+ cells in the lungs from a CD11c-/SiglecF+ progenitor population within four weeks after transplantation. Based on these data, we suggest hematopoietic stem cell-based gene therapy as an effective and cause-directed treatment approach for herPAP.

    DOI: 10.3324/haematol.2018.214866

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  • Serum Anti-interferon-γ Autoantibody Titer as a Potential Biomarker of Disseminated Non-tuberculous Mycobacterial Infection 査読 国際誌

    Kazutaka Yoshizawa, Ami Aoki, Kenjiro Shima, Yoshinari Tanabe, Toshiyuki Koya, Takashi Hasegawa, Toshiaki Kikuchi, Takuro Sakagami

    Journal of Clinical Immunology   40 ( 2 )   399 - 405   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    PURPOSE: In the past decade, the relationship between naturally occurring interferon-γ-neutralizing autoantibodies (IFNγ-Ab) and disseminated non-tuberculous mycobacteria (NTM) infection has been established. Furthermore, immune suppressive therapy aimed at the suppression of antibody production has shown efficacy as a supportive treatment. However, the nature of antibody behavior and antibody titer during the course of this disease, as well as the pathophysiological significance of IFNγ-Ab, has not yet been fully elucidated. METHODS: Thirteen Japanese subjects suffering from disseminated NTM (dNTM) infection with IFNγ-Ab were evaluated. The fluctuation of IFNγ-Ab titer and the neutralizing capacity against IFN-γ during the course of the disease were retrospectively analyzed. IFNγ-Ab titers in the sera were quantified using an enzyme-linked immunosorbent assay; neutralizing capacity was evaluated via flow cytometry. RESULTS: Serum antibody titers were not constant during the treatment period and varied over the course of the disease. The antibody titer decreased when the disease was improved by anti-mycobacterial treatment (p < 0.01) and increased as the disease progressed (p < 0.05). Even after the antibody titer decreased, the neutralizing capacity against IFN-γ was maintained by individual sera. CONCLUSIONS: Despite the improvement in the pathological condition via treatment, the patients' sera maintained neutralizing capacity against IFN-γ. Antibody titer fluctuated over the course of the disease and exhibited potential as a biomarker for judgment of the disease state.

    DOI: 10.1007/s10875-020-00762-1

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    その他リンク: http://link.springer.com/article/10.1007/s10875-020-00762-1/fulltext.html

  • Long-Term Safety and Efficacy of Gene-Pulmonary Macrophage Transplantation Therapy of PAP in Csf2ra−/− Mice 査読 国際誌

    Paritha Arumugam, Takuji Suzuki, Kenjiro Shima, Cormac McCarthy, Anthony Sallese, Matthew Wessendarp, Yan Ma, Johann Meyer, Diane Black, Claudia Chalk, Brenna Carey, Nico Lachmann, Thomas Moritz, Bruce C. Trapnell

    Molecular Therapy   27 ( 9 )   1597 - 1611   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    Hereditary pulmonary alveolar proteinosis (PAP) is a genetic lung disease characterized by surfactant accumulation and respiratory failure arising from disruption of GM-CSF signaling. While mutations in either CSF2RA or CSF2RB (encoding GM-CSF receptor α or β chains, respectively) can cause PAP, α chain mutations are responsible in most patients. Pulmonary macrophage transplantation (PMT) is a promising new cell therapy in development; however, no studies have evaluated this approach for hereditary PAP (hPAP) caused by Csf2ra mutations. Here, we report on the preclinical safety, tolerability, and efficacy of lentiviral-vector (LV)-mediated Csf2ra expression in macrophages and PMT of gene-corrected macrophages (gene-PMT therapy) in Csf2ra gene-ablated (Csf2ra-/-) mice. Gene-PMT therapy resulted in a stable transgene integration and correction of GM-CSF signaling and functions in Csf2ra-/- macrophages in vitro and in vivo and resulted in engraftment and long-term persistence of gene-corrected macrophages in alveoli; restoration of pulmonary surfactant homeostasis; correction of PAP-specific cytologic, histologic, and biomarker abnormalities; and reduced inflammation associated with disease progression in untreated mice. No adverse consequences of gene-PMT therapy in Csf2ra-/- mice were observed. Results demonstrate that gene-PMT therapy of hPAP in Csf2ra-/- mice was highly efficacious, durable, safe, and well tolerated.

    DOI: 10.1016/j.ymthe.2019.06.010

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  • Statin as a novel pharmacotherapy of pulmonary alveolar proteinosis 査読

    Cormac McCarthy, Elinor Lee, James P. Bridges, Anthony Sallese, Takuji Suzuki, Jason C. Woods, Brian J. Bartholmai, Tisha Wang, Claudia Chalk, Brenna C. Carey, Paritha Arumugam, Kenjiro Shima, Elizabeth J. Tarling, Bruce C. Trapnell

    Nature Communications   9 ( 1 )   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1038/s41467-018-05491-z

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    その他リンク: http://www.nature.com/articles/s41467-018-05491-z

  • Clinical Significance of Interferon-γ Neutralizing Autoantibodies Against Disseminated Nontuberculous Mycobacterial Disease 査読 国際誌

    Ami Aoki, Takuro Sakagami, Kazutaka Yoshizawa, Kenjiro Shima, Mio Toyama, Yoshinari Tanabe, Hiroshi Moro, Nobumasa Aoki, Satoshi Watanabe, Toshiyuki Koya, Takashi Hasegawa, Kozo Morimoto, Atsuyuki Kurashima, Yoshihiko Hoshino, Bruce C Trapnell, Toshiaki Kikuchi

    Clinical Infectious Diseases   66 ( 8 )   1239 - 1245   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    Background: Interferon-γ neutralizing autoantibodies (nIFNγ-autoAbs) are reported in patients with disseminated nontuberculous mycobacteria (NTM) infection and may function by increasing the infection risk. Notwithstanding, the prevalence of nIFNγ-autoAbs as well as the clinical presentation, diagnosis, and natural history of disseminated NTM infection in these patients is poorly understood. Methods: In this retrospective observational study, data and sera for 331 Japanese subjects with mycobacterial infection were collected and analyzed. IFNγ-autoAb titers in sera were quantified using an enzyme-linked immunosorbent assay; neutralizing capacity was evaluated via flow cytometry. Results: Disseminated NTM was identified in 50 human immunodeficiency virus-uninfected patients. Of these, 30 of 37 (81%) immunocompetent patients had an increased nIFNγ-autoAb titer whereas only 1 of 13 (7.7%) immunodeficient patients had an increased nIFNγ-autoAb titer (P < .0001, χ2 test). Presenting symptoms were nonspecific and NTM infection was not included in the differential diagnosis in most cases. All patients with disseminated NTM and an increased serum nIFNγ-autoAb level received prolonged antimicrobial therapy. In 6 cases when antibiotic treatment was discontinued, NTM infection recurred and required resumption of antibiotic therapy for infection control. The mortality rate was 3.2% in disseminated NTM patients with nIFNγ-autoAbs and 21% in those without. Conclusions: nIFNγ-autoAbs were present in most patients with disseminated NTM infection without a diagnosis of clinical immunodeficiency. Diagnosis of disseminated NTM requires a high degree of suspicion and can be improved by measuring serum nIFNγ-autoAb titer. Long-term antibiotic therapy helps prevent recrudescent NTM infection.

    DOI: 10.1093/cid/cix996

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  • Targeting cholesterol homeostasis in lung diseases 査読

    Anthony Sallese, Takuji Suzuki, Cormac McCarthy, James Bridges, Alyssa Filuta, Paritha Arumugam, Kenjiro Shima, Yan Ma, Matthew Wessendarp, Diane Black, Claudia Chalk, Brenna Carey, Bruce C. Trapnell

    Scientific Reports   7 ( 1 )   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1038/s41598-017-10879-w

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    その他リンク: http://www.nature.com/articles/s41598-017-10879-w

  • Inhibition of IRAK1 Ubiquitination Determines Glucocorticoid Sensitivity for TLR9-Induced Inflammation in Macrophages 査読

    Fansheng Kong, Zhiwei Liu, Viral G. Jain, Kenjiro Shima, Takuji Suzuki, Louis J. Muglia, Daniel T. Starczynowski, Chandrashekhar Pasare, Sandip Bhattacharyya

    The Journal of Immunology   199 ( 10 )   3654 - 3667   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:The American Association of Immunologists  

    DOI: 10.4049/jimmunol.1700443

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  • Effects of sublingual immunotherapy in a murine asthma model sensitized by intranasal administration of house dust mite extracts 査読 国際誌

    Kenjiro Shima, Toshiyuki Koya, Keisuke Tsukioka, Takuro Sakagami, Takashi Hasegawa, Chiharu Fukano, Katsuyo Ohashi-Doi, Satoshi Watanabe, Eiichi Suzuki, Toshiaki Kikuchi

    Allergology International   66 ( 1 )   89 - 96   2017年1月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    BACKGROUND: Sublingual immunotherapy (SLIT) has received attention as a method for allergen immunotherapy. However, the mechanism of SLIT has not yet been fully investigated. Therefore, we evaluated the effects of SLIT in a murine asthma model, sensitized by intranasal administration of house dust mite (HDM) extracts. METHODS: Female BALB/c mice were intranasally exposed to HDM for either 3 or 5 weeks (5 consecutive days per week). Mice were administered either low-dose (0.5 mg/day) or high-dose (5 mg/day) sublingual HDM extracts for 2 weeks, followed by an additional week of intranasal exposure. Airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF) cell count, cytokine levels in the BALF and lymph node cell culture supernatants, and allergen-specific antibodies were measured. Lung histology was also investigated. RESULTS: In mice sensitized for 5 weeks, high-dose SLIT ameliorated AHR, airway eosinophilia and goblet cell metaplasia. In mice sensitized for 3 weeks, even low dose SLIT ameliorated AHR and airway eosinophilia. Th2 cytokine levels in culture supernatants of submandibular lymph node cells in high-dose SLIT mice decreased, whereas IL-10 levels increased. Total IgA in BALF increased in mice sensitized for 3 or 5 weeks, and high-dose SLIT also increased allergen-specific IgG2a in mice sensitized for 5 weeks. CONCLUSIONS: These data suggest that earlier induction of SLIT in HDM-sensitized mice provides superior suppression of AHR and goblet cell metaplasia. The modulation of allergen specific IgG2a and local IgA might play a role in the amelioration of AHR and airway inflammation.

    DOI: 10.1016/j.alit.2016.05.012

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  • 抗IFN-γ自己抗体陽性播種性非結核性抗酸菌症の臨床表現型

    青木 亜美, 坂上 拓郎, 島 賢治郎, 青木 信将, 茂呂 寛, 田邊 嘉也, 小屋 俊之, 菊地 利明

    結核   91 ( 3 )   401 - 401   2016年3月

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    記述言語:日本語   出版者・発行元:(一社)日本結核・非結核性抗酸菌症学会  

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  • 非結核性抗酸菌症の今日的問題 抗IFN-γ自己抗体価と播種性非結核性抗酸菌症の病勢に関する検討

    青木 亜美, 坂上 拓郎, 島 賢治郎, 茂呂 寛, 田邊 嘉也, 小屋 俊之, 各務 博, 菊地 利明, 長谷 衣佐乃, 神白 麻衣子, 田中 健之, 小泉 祐介, 田村 厚久

    日本呼吸器学会誌   5 ( 増刊 )   147 - 147   2016年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • Characteristics of eosinophilic and non-eosinophilic asthma during treatment with inhaled corticosteroids 査読 国際誌

    Toshiki Furukawa, Takuro Sakagami, Toshiyuki Koya, Takashi Hasegawa, Hidenori Kawakami, Yosuke Kimura, Yoshifumi Hoshino, Hirotaka Sakamoto, Kenjiro Shima, Keisuke Tsukioka, Mio Toyama, Masachika Hayashi, Hiroshi Kagamu, Ei-ichi Suzuki, Ichiei Narita

    Journal of Asthma   52 ( 4 )   417 - 422   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Informa UK Limited  

    OBJECTIVE: Eosinophilic inflammation in the respiratory tract is a hallmark of bronchial asthma. In naïve cases, the inflammatory profile is associated with disease severity and reactivity to inhaled corticosteroids (ICS). Sustained airway eosinophilia has been reported during ICS treatment. However, the immunological characteristics of these cases are not known and it is unclear if this situation contributes to asthma control. This study was performed to determine the answer of these questions. METHODS: To compare phenotypes of eosinophilic and non-eosinophilic asthma (EA and NEA, respectively) under ICS treatment, clinical data were obtained from asthmatic subjects (n = 22) and healthy controls (n = 10), and the leukocyte compositions of induced sputum and peripheral blood were determined. T lymphocyte profiles in systemic blood were assessed by flow cytometry. RESULTS: A higher frequency of emergency room visits was observed in the NEA group, which had a higher neutrophil count relative to the total inflammatory cell population in induced sputum than the EA group (59.5 versus 36.6%; p < 0.01). The fraction of helper T (Th)17 lymphocytes as well as the ratio of Th17 to regulatory T cells (Treg) in the peripheral blood was higher in the NEA than in the EA group (0.24 versus 0.13; p < 0.05). CONCLUSIONS: Th17 were more prevalent than Treg cells in the peripheral blood of NEA patients under ICS treatment, corresponding to neutrophil-dominant airway inflammation and a severe asthmatic phenotype. Thus, an imbalance in Th17/Treg may be associated with the pathogenesis of NEA in patients undergoing ICS treatment.

    DOI: 10.3109/02770903.2014.975357

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  • ミコフェノール酸モフェチルを含む3剤併用療法を行った皮膚筋炎合併間質性肺疾患の1例

    島 賢治郎, 坂上 拓郎, 市川 紘将, 穂苅 諭, 朝川 勝明, 小屋 俊之, 各務 博, 高田 俊範, 成田 一衛

    日本呼吸器学会誌   4 ( 1 )   76 - 80   2015年1月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

    症例は29歳、女性。特徴的な皮疹、乏しい筋症状、抗CADM-140/MDA5抗体陽性から、clinically amyopathic dermatomyositis(CADM)と診断した。間質性肺疾患の合併も認めたため、プレドニゾロン、シクロスポリンに加え、免疫抑制剤であるミコフェノール酸モフェチル(mycophenolate mofetil:MMF)を用い、良好な転帰を得た。病勢とともに、抗CADM-140/MDA5抗体価は低下した。本疾患におけるMMFを用いた治療例は報告が少なく、貴重な症例と考え報告する。(著者抄録)

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    その他リンク: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J05953&link_issn=&doc_id=20150203210012&doc_link_id=%2Fci6respo%2F2015%2F000401%2F014%2F0076-0080%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fci6respo%2F2015%2F000401%2F014%2F0076-0080%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • The Effects of All-Trans Retinoic Acid on the Induction of Oral Tolerance in a Murine Model of Bronchial Asthma 査読 国際誌

    Hirotaka Sakamoto, Toshiyuki Koya, Keisuke Tsukioka, Kenjiro Shima, Satoshi Watanabe, Hiroshi Kagamu, Yosuke Kimura, Takuro Sakagami, Takashi Hasegawa, Eiichi Suzuki, Ichiei Narita

    International Archives of Allergy and Immunology   167 ( 3 )   167 - 176   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:S. Karger AG  

    BACKGROUND: Active suppression induced by regulatory T (Treg) cells is reported to be one of the mechanisms involved in oral tolerance. All-trans retinoic acid (ATRA) has been reported to affect Treg cell differentiation. The present study examined the effects of ATRA on the induction of oral tolerance in a murine model of bronchial asthma. METHODS: BALB/c mice were sensitized to and challenged with ovalbumin (OVA) through feeding followed by OVA challenges. In some study groups ATRA was orally administered concomitantly with OVA feeding either in the presence or absence of the retinoic acid receptor antagonist LE135. Lung CD4+ T cells were isolated from mice exposed to ATRA and/or OVA, and transferred to control mice. Airway hyperresponsiveness (AHR), cell counts and cytokine levels in bronchoalveolar lavage (BAL) fluid, and lung histology were assessed. RESULTS: Concomitant administration of ATRA with OVA ameliorated AHR, airway eosinophilia, elevation of cytokines in BAL fluid and goblet cell metaplasia. The proportion of Treg cells in the lungs was increased in mice treated with OVA and ATRA, as compared to those treated with OVA only. Transfer of lung CD4+ T cells from mice treated with OVA and ATRA induced suppression of AHR and airway inflammation. LE135 completely reversed the effects of ATRA on AHR, airway allergic inflammation and the number of Treg cells in the lungs. CONCLUSION: These data suggested that oral administration of ATRA with OVA had the potential to enhance oral tolerance in this murine model of bronchial asthma. These effects were mediated, at least in part, by Treg cell expansion.

    DOI: 10.1159/000437326

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  • 抗Interferon-γ中和自己抗体陽性の播種性非結核性抗酸菌症の検討

    坂上 拓郎, 島 賢治郎, 田邊 嘉也, 青木 信将, 茂呂 寛, 長谷川 隆志, 成田 一衛

    日本化学療法学会雑誌   62 ( Suppl.A )   388 - 388   2014年5月

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    記述言語:日本語   出版者・発行元:(公社)日本化学療法学会  

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  • オマリズマブ導入による気管支喘息及び鼻・副鼻腔疾患の治療効果

    黒川 允, 小屋 俊之, 月岡 啓輔, 外山 美央, 島 賢治郎, 坂上 拓郎, 長谷川 隆志, 鈴木 栄一, 成田 一衛, 野村 智幸, 高橋 姿

    アレルギー   63 ( 3-4 )   571 - 571   2014年4月

  • インフルエンザワクチン接種後に好酸球性血管浮腫を来した1例

    林 正周, 小屋 俊之, 月岡 啓輔, 外山 美央, 島 賢治郎, 黒川 允, 坂上 拓郎, 下村 尚子, 長谷川 隆志, 鈴木 栄一, 成田 一衛

    アレルギー   63 ( 3-4 )   616 - 616   2014年4月

  • 吸入ステロイド単剤に効果不十分なアスリートの喘息症例における追加薬剤の効果について

    小屋 俊之, 月岡 啓輔, 島 賢治郎, 外山 美央, 黒川 允, 林 正周, 坂上 拓郎, 長谷川 隆志, 鈴木 栄一, 荒川 正昭, 成田 一衛

    アレルギー   63 ( 3-4 )   577 - 577   2014年4月

  • Cluster analysis identifies characteristic phenotypes of asthma with accelerated lung function decline 査読 国際誌

    Takuro Sakagami, Takashi Hasegawa, Toshiyuki Koya, Toshiki Furukawa, Hidenori Kawakami, Yosuke Kimura, Yoshifumi Hoshino, Hirotaka Sakamoto, Kenjiro Shima, Hiroshi Kagamu, Ei-ichi Suzuki, Ichiei Narita

    Journal of Asthma   51 ( 2 )   113 - 118   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Informa UK Limited  

    OBJECTIVE: While the majority of individuals with asthma retain normal lung function over time, some exhibit accelerated lung function decline. Preservation of lung function is an important aspect of asthma management. Whether the asthma guidelines can prevent lung function decline remains controversial. This study was performed to determine the distribution of asthmatic subjects with greater lung function decline and to identify characteristic clinical features of such subjects treated in accordance with clinical guidelines by using hierarchical cluster analysis. METHODS: Eighty-six asthmatic subjects without a history of smoking were assessed with respect to eight variables selected from clinical phenotypes by using step-wise multiple regression analysis. Hierarchical cluster analysis using Ward's method generated a dendrogram for estimation of the number of clusters within the population and the differences between them. RESULTS: Three distinct clusters were identified. Cluster 1 (n = 40) comprised women with late-onset asthma. Cluster 2 (n = 17) comprised subjects with early-onset asthma, atopy and long disease duration. Cluster 3 (n = 29) predominantly comprised older men who had late-onset asthma, a lower prevalence of exacerbation and a lower predicted % forced expiratory volume in 1 s (FEV1) at baseline. Subjects in cluster 3 showed a mean decline in FEV1 of 69 mL/year, which was the greatest lung function decline among the three clusters. CONCLUSION: We identified a subgroup of patients with accelerated lung function decline despite appropriate asthma treatment based on guidelines constructed by using subjective symptoms.

    DOI: 10.3109/02770903.2013.852201

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  • 臨床情報によるクラスター解析から見出された喘息における呼吸機能低下が促進される群の表現型

    坂上 拓郎, 長谷川 隆志, 小屋 俊之, 林 正周, 島 賢治郎, 黒川 允, 外山 美央, 月岡 啓輔, 鈴木 栄一, 成田 一衛

    日本呼吸器学会誌   3 ( 増刊 )   329 - 329   2014年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • 抗Interferon-γ中和自己抗体陽性の播種性非結核性抗酸菌症 新たな疾患概念

    島 賢治郎, 坂上 拓郎, 青木 信将, 茂呂 寛, 田邊 嘉也, 各務 博, 長谷川 隆志, 高田 俊範, 成田 一衛

    日本内科学会雑誌   103 ( Suppl. )   229 - 229   2014年2月

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    記述言語:日本語   出版者・発行元:(一社)日本内科学会  

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  • Novel assay to detect increased level of neutralizing anti-interferon gamma autoantibodies in non-tuberculous mycobacterial patients 査読 国際誌

    Kenjiro Shima, Takuro Sakagami, Yoshinari Tanabe, Nobumasa Aoki, Hiroshi Moro, Toshiyuki Koya, Hiroshi Kagamu, Takashi Hasegawa, Ei-ichi Suzuki, Ichiei Narita

    Journal of Infection and Chemotherapy   20 ( 1 )   52 - 56   2014年1月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    Subjects exposed to non-tuberculous mycobacterium (NTM) species do not always develop an active disease, which likely reflects underlying host susceptibility factors. Recent reports have shown that anti interferon gamma (IFN-γ) neutralizing autoantibodies (IFN-γ Ab) are associated with the development of disseminated NTM in patients without known evidence of immunodeficiency. The purpose of this study is to establish the screening method if subjects have IFN-γ Ab. Whole blood was obtained from patients with disseminated NTM, those with pulmonary NTM, and healthy controls. The neutralizing capacity to IFN-γ activity was assessed as an inhibition of Signal Transducer and Activation of Transcription 1 (STAT-1) phosphorylation in leukocyte after stimulation with exogenous IFN-γ by flow cytometer. The strength of phosphorylation was described as STAT1 phosphorylation index. Antigen capture assay was performed to measure the relative titer of Immunoglobulin-G fraction of IFN-γ Ab. STAT1 phosphorylation by IFN-γ was significantly inhibited in the leukocytes from patients with disseminated NTM compared to that in healthy subjects, while this inhibition was not observed in patients with pulmonary NTM. All subjects with inhibited STAT1 phosphorylation had high titer of Immunoglobulin-G that reacted with IFN-γ in the antigen capture assay. The measurement of STAT1 phosphorylation index in whole blood leukocytes and antigen capture assay are simple and useful method for detection of anti-IFN-γ neutralizing autoantibodies, and is valuable in the pathophysiological diagnosis of disseminated NTM patients without obvious immunodeficiency.

    DOI: 10.1016/j.jiac.2013.08.003

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  • A single injection of a sustained-release prostacyclin analog (ONO-1301MS) suppresses airway inflammation and remodeling in a chronic house dust mite-induced asthma model 査読 国際誌

    Yosuke Kimura, Toshiyuki Koya, Hiroshi Kagamu, Kenjiro Shima, Hirotaka Sakamoto, Hidenori Kawakami, Yoshifumi Hoshino, Toshiki Furukawa, Takuro Sakagami, Takashi Hasegawa, Masami Narita, Eiichi Suzuki, Ichiei Narita

    European Journal of Pharmacology   721 ( 1-3 )   80 - 85   2013年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    ONO-1301, a novel prostacyclin agonist with thromboxane A2 synthase inhibitory activity, is a useful agent for ameliorating airway allergic inflammation; however, its short-action feature implies a requirement for the frequent administration of this drug. Therefore, we investigated the effects of ONO-1301-loaded poly (d,l-lactic-co-glycolic acid) microspheres (ONO-1301MS; to release ONO-1301 for 3 weeks) on the airway inflammation and remodeling in chronic house dust mite (HDM)-induced model. Balb/c mice were exposed to an HDM extract intranasally for 5 days/week for 5 consecutive weeks. The mice received a single subcutaneous injection of ONO-1301MS or vehicle after 3 weeks of HDM exposure, followed by 2 additional weeks of HDM exposure. Forty-eight hours after the last HDM exposure, airway hyperresponsiveness to methacholine was assessed and bronchoalveolar lavage was performed. Lung specimens were excised and stained to check for goblet cell metaplasia, airway smooth muscle hypertrophy, and submucosal fibrosis. Mice receiving ONO-1301MS showed significantly lower airway hyperresponsiveness, airway eosinophilia, and induced T helper 2 cytokine production compared with mice receiving the vehicle. Histological findings such as goblet cell metaplasia, airway smooth muscle hypertrophy, and submucosal fibrosis were decreased in ONO-1301MS-treated mice compared with vehicle-treated mice. A single administration of ONO-1301MS achieved sustained elevation of its circulating level for 3 weeks. These data suggest that a single administration of ONO-1301MS may suppress airway hyperresponsiveness, airway allergic inflammation, and development of airway remodeling in chronic HDM-induced asthma model. This agent may be effective as an anti-inflammatory and remodeling drug in the practical treatment of asthma.

    DOI: 10.1016/j.ejphar.2013.09.051

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  • ダニ抗原点鼻喘息モデルにおける感作期間と舌下免疫療法有効性の検討

    島 賢治郎, 小屋 俊之, 月岡 啓輔, 外山 美央, 坂元 宏隆, 黒川 允, 坂上 拓郎, 長谷川 隆志, 土井 雅津代, 杜 偉彬, 鈴木 栄一, 成田 一衛

    アレルギー   62 ( 9-10 )   1353 - 1353   2013年10月

  • オマリズマブ使用にて、慢性副鼻腔炎の改善も認めた難治性気管支喘息の一例

    黒川 允, 小屋 俊之, 島 賢治郎, 月岡 啓輔, 外山 美央, 坂上 拓郎, 長谷川 隆志, 鈴木 栄一, 成田 一衛

    アレルギー   62 ( 9-10 )   1342 - 1342   2013年10月

  • アスリートの喘息における呼吸機能、気道過敏性およびバイオマーカーの特徴

    小屋 俊之, 月岡 啓輔, 島 賢治郎, 外山 美央, 黒川 允, 林 正周, 坂上 拓郎, 長谷川 隆志, 荒川 正昭, 鈴木 栄一, 成田 一衛

    アレルギー   62 ( 9-10 )   1390 - 1390   2013年10月

  • アスリート喘息症例におけるブデソニド/ホルモテロール配合剤の効果

    小屋 俊之, 月岡 啓輔, 島 賢治郎, 外山 美央, 坂元 宏隆, 星野 芳史, 坂上 拓郎, 古川 俊貴, 長谷川 隆志, 鈴木 栄一, 荒川 正昭, 成田 一衛

    アレルギー   62 ( 3-4 )   402 - 402   2013年4月

  • ステロイド使用後に再燃した反復性好酸球性血管浮腫の一例

    月岡 啓輔, 小屋 俊之, 島 賢治郎, 外山 美央, 坂元 宏隆, 坂上 拓郎, 古川 俊貴, 長谷川 隆志, 鈴木 栄一, 成田 一衛

    アレルギー   62 ( 3-4 )   412 - 412   2013年4月

  • 播種性非結核性抗酸菌症における抗IFNγ自己抗体検出法の確立

    島 賢治郎, 坂上 拓郎, 青木 信将, 茂呂 寛, 田邊 嘉也, 鈴木 栄一, 成田 一衛, 桑原 克弘

    日本呼吸器学会誌   2 ( 増刊 )   313 - 313   2013年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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受賞

  • 日本肺サーファクタント・界面医学会第56回学術研究会学会奨励賞

    2020年8月   日本肺サーファクタント・界面医学会   Csf2ra遺伝子欠損マウスの樹立: 遺伝性肺胞蛋白症モデル

    島賢治郎, 菊地利明, Bruce Trapnell, 鈴木拓児

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  • ATS 2019 International Conference, Abstract Scholarship Award

    2019年5月   American Thoracic Society   CRISPR/Cas9 Genome Editing Therapy for Hereditary Pulmonary Alveolar Proteinosis

    Kenjiro Shima

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  • International Rare Lung Diseases Research Conference 2018, Best Poster Award

    2018年9月   Rare Lung Diseases Consortium   Long-term Evaluation of Pulmonary Macrophage Transplantation Therapy in Csf2ra Gene-Deficient Mice, a Clinically Relevant Model of Hereditary Pulmonary Alveolar Proteinosis.

    Kenjiro Shima, Takuji Suzuki, Paritha Arumugam, Nico Lachmann, Thomas Moritz, Yan Ma, Dianna Black, Claudia Chalk, Brenna Carey, Bruce C Trapnell

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  • 平成24年度日本感染症学会東日本地方会奨励賞(臨床)

    2012年10月   日本感染症学会   播種性非結核性抗酸菌症における抗IFNγ自己抗体検出法の確立

    島 賢治郎, 坂上 拓郎, 成田 一衛, 青木 信将, 茂呂 寛, 田邊 嘉也, 鈴木 栄一, 桑原 克弘

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共同研究・競争的資金等の研究

  • 自己免疫性肺胞蛋白症の病態におけるIgA型抗GM-CSF自己抗体の関与について

    研究課題/領域番号:20K22759  2020年9月 - 2022年3月

    日本学術振興会  科学研究費助成事業 研究活動スタート支援  研究活動スタート支援

    島 賢治郎

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    配分額:2860000円 ( 直接経費:2200000円 、 間接経費:660000円 )

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