start-ver=1.4
cd-journal=joma
no-vol=136
cd-vols=
no-issue=2
article-no=
start-page=63
end-page=68
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Metformin-induced mitochondrial reactive oxygen species and host defense mechanisms
kn-title=メトホルミンによるミトコンドリア活性酸素誘導と生体防御機構
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=鵜殿平一郎
kn-aut-sei=鵜殿
kn-aut-mei=平一郎
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Department of Immunology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学学術研究院医歯薬学域　免疫学
en-keyword=CD8T 細胞
kn-keyword=CD8T 細胞
en-keyword=活性酸素
kn-keyword=活性酸素
en-keyword=Nrf2
kn-keyword=Nrf2
en-keyword=解糖系
kn-keyword=解糖系
en-keyword=ミトコンドリア
kn-keyword=ミトコンドリア
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=15
article-no=
start-page=5028
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230731
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Evidence for Hypoxia-Induced Shift in ATP Production from Glycolysis to Mitochondrial Respiration in Pulmonary Artery Smooth Muscle Cells in Pulmonary Arterial Hypertension
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: The metabolic state of pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) is not well understood. In this study, we examined the balance between glycolysis and mitochondrial respiration in non-PAH-PASMCs and PAH-PASMCs under normoxia and hypoxia. Methods: We investigated the enzymes involved in glycolysis and mitochondrial respiration, and studied the two major energy-yielding pathways (glycolysis and mitochondrial respiration) by measuring extracellular acidification rate (ECAR) and cellular oxygen consumption rate (OCR) using the Seahorse extracellular flux technology. Results: Under both normoxia and hypoxia, the mRNA and protein levels of pyruvate dehydrogenase kinase 1 and pyruvate dehydrogenase were increased in PAH-PASMCs compared with non-PAH-PASMCs. The mRNA and protein levels of lactate dehydrogenase, as well as the intracellular lactate concentration, were also increased in PAH-PASMCs compared with non-PAH-PASMCs under normoxia. However, these were not significantly increased in PAH-PASMCs compared with non-PAH-PASMCs under hypoxia. Under normoxia, ATP production was significantly lower in PAH-PASMCs (59 ± 5 pmol/min) than in non-PAH-PASMCs (70 ± 10 pmol/min). On the other hand, ATP production was significantly higher in PAH-PASMCs (31 ± 5 pmol/min) than in non-PAH-PASMCs (14 ± 3 pmol/min) under hypoxia. Conclusions: There is an underlying change in the metabolic strategy to generate ATP production under the challenge of hypoxia.
en-copyright=
kn-copyright=

en-aut-name=AkagiSatoshi
en-aut-sei=Akagi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NakamuraKazufumi
en-aut-sei=Nakamura
en-aut-mei=Kazufumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KondoMegumi
en-aut-sei=Kondo
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HirohataSatoshi
en-aut-sei=Hirohata
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NishidaMikako
en-aut-sei=Nishida
en-aut-mei=Mikako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SaitoYukihiro
en-aut-sei=Saito
en-aut-mei=Yukihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YoshidaMasashi
en-aut-sei=Yoshida
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MiyoshiToru
en-aut-sei=Miyoshi
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=ItoHiroshi
en-aut-sei=Ito
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=glycolysis
kn-keyword=glycolysis
en-keyword=mitochondrial respiration
kn-keyword=mitochondrial respiration
en-keyword=pulmonary arterial hypertension
kn-keyword=pulmonary arterial hypertension
en-keyword=pulmonary artery smooth muscle cells
kn-keyword=pulmonary artery smooth muscle cells
en-keyword=Seahorse technology
kn-keyword=Seahorse technology
en-keyword=hypoxia
kn-keyword=hypoxia
en-keyword=ATP production
kn-keyword=ATP production
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=
article-no=
start-page=864225
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220629
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Nutrient Condition in the Microenvironment Determines Essential Metabolisms of CD8(+) T Cells for Enhanced IFN gamma Production by Metformin
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Metformin (Met), a first-line drug for type 2 diabetes, lowers blood glucose levels by suppressing gluconeogenesis in the liver, presumably through the liver kinase B1-dependent activation of AMP-activated protein kinase (AMPK) after inhibiting respiratory chain complex I. Met is also implicated as a drug to be repurposed for cancers; its mechanism is believed identical to that of gluconeogenesis inhibition. However, AMPK activation requires high Met concentrations at more than 1 mM, which are unachievable in vivo. The immune-mediated antitumor response might be the case in a low dose Met. Thus, we proposed activating or expanding tumor-infiltrating CD8(+) T cells (CD8TILs) in a mouse model by orally administering Met in free drinking water. Here we showed that Met, at around 10 mu M and a physiologically relevant concentration, enhanced production of IFN gamma,TNF alpha and expression of CD25 of CD8(+) T cells upon TCR stimulation. Under a glucose-rich condition, glycolysis was exclusively involved in enhancing IFN gamma production. Under a low-glucose condition, fatty acid oxidation or autophagy-dependent glutaminolysis, or both, was also involved. Moreover, phosphoenolpyruvate carboxykinase 1 (PCK1), converting oxaloacetate to phosphoenolpyruvate, became essential. Importantly, the enhanced IFN gamma production was blocked by a mitochondrial ROS scavenger and not by an inhibitor of AMPK. In addition, IFN gamma production by CD8TILs relied on pyruvate translocation to the mitochondria and PCK1. Our results revealed a direct effect of Met on IFN gamma production of CD8(+) T cells that was dependent on differential metabolic pathways and determined by nutrient conditions in the microenvironment.
en-copyright=
kn-copyright=

en-aut-name=ChaoRuoyu
en-aut-sei=Chao
en-aut-mei=Ruoyu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishidaMikako
en-aut-sei=Nishida
en-aut-mei=Mikako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=YamashitaNahoko
en-aut-sei=Yamashita
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TokumasuMiho
en-aut-sei=Tokumasu
en-aut-mei=Miho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ZhaoWeiyang
en-aut-sei=Zhao
en-aut-mei=Weiyang
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KudoIkuru
en-aut-sei=Kudo
en-aut-mei=Ikuru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=CD8+T lymphocytes
kn-keyword=CD8+T lymphocytes
en-keyword=glycolysis
kn-keyword=glycolysis
en-keyword=FAO
kn-keyword=FAO
en-keyword=glutaminolysis
kn-keyword=glutaminolysis
en-keyword=IFNg
kn-keyword=IFNg
en-keyword=autophagy plus T
kn-keyword=autophagy plus T
en-keyword=metformin
kn-keyword=metformin
END

start-ver=1.4
cd-journal=joma
no-vol=1866
cd-vols=
no-issue=8
article-no=
start-page=130171
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202208
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Metformin-ROS-Nrf2 connection in the host defense mechanism against oxidative stress, apoptosis, cancers, and ageing
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Reactive oxygen species (ROS) acts as a second messenger to trigger biological responses in low concentrations, while it is implicated to be toxic to biomolecules in high concentrations. Mild inhibition of respiratory chain Complex I by metformin at physiologically relevant concentrations stimulates production of low-level mitochondrial ROS. The ROS seems to induce anti-oxidative stress response via activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase (GPx), which results in not only elimination of ROS but also activation of cellular responses including resistance to apoptosis, metabolic changes, cell proliferation, senescence prevention, lifespan extension, and immune T cell activation against cancers, regardless of its effect controlling blood glucose level and T2DM. Although metformin's effect against T2DM, cancers, and ageing, are believed mostly attributed to the activation of AMP-activated protein kinase (AMPK), the cellular responses involving metformin-ROS-Nrf2 axis might be another natural asset to improve healthspan and lifespan.
en-copyright=
kn-copyright=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishidaMikako
en-aut-sei=Nishida
en-aut-mei=Mikako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Mitochondrial ROS
kn-keyword=Mitochondrial ROS
en-keyword=Oxidative stress
kn-keyword=Oxidative stress
en-keyword=Apoptosis
kn-keyword=Apoptosis
en-keyword=Ageing
kn-keyword=Ageing
en-keyword=Nrf2
kn-keyword=Nrf2
END

start-ver=1.4
cd-journal=joma
no-vol=34
cd-vols=
no-issue=6
article-no=
start-page=293
end-page=302
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202228
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Blocking EP4 downregulates tumor metabolism and synergizes with anti-PD-1 therapy to activate natural killer cells in a lung adenocarcinoma model
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Prostaglandin E2 (PGE2), a product of the cyclooxygenase (COX) pathway, is produced by tumors and surrounding stromal cells. It stimulates tumor progression, promotes angiogenesis, and suppresses the antitumor response. Pharmacological inhibition of PGE2 synthesis has been shown to suppress tumor initiation and growth in vivo. In the current study, we demonstrated that the growth of the Ptgs2-deficient the 3LL lung adenocarcinoma cell line was downregulated in vivo through natural killer (NK) cell activation and a reduction in the population of polymorphonuclear leukocyte-myeloid-derived suppressor cells (PMN-MDSCs) and tumor associated macrophages (TAMs). Based on these results, the therapeutic effect of ONO-AE3?208 (EP4i), an inhibitor of EP4 (a PGE2 receptor), combined with anti-PD-1Ab was evaluated. EP4i, but not anti-PD-1 Ab, decreased tumor metabolism including glycolysis, fatty acid oxidation, and oxidative phosphorylation. EP4i induced IFNγ production from only NK cells (not from T cells) and a shift from M2- to M1-like macrophages in TAMs. These effects were further enhanced by anti-PD-1 Ab treatment. Although CD8T cell infiltration was increased, IFNγ production was not significantly altered, even with combination therapy. Tumor hypoxia was ameliorated by either EP4i or anti-PD-1 Ab treatment, which was further affected by the combination. Normalization of tumor vessels was significant only for the combination therapy. The results indicate a novel effect of EP4i for the metabolic reprogramming of tumors, revealed unique features of EP4i that can synergize with anti-PD-1Ab to promote IFNγ production of NK cells, polarize TAMs into the M1-phenotype, and reduce hypoxia through normalization of the tumor vasculature. 
en-copyright=
kn-copyright=

en-aut-name=TokumasuMiho
en-aut-sei=Tokumasu
en-aut-mei=Miho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishidaMikako
en-aut-sei=Nishida
en-aut-mei=Mikako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KawaguchiTakamasa
en-aut-sei=Kawaguchi
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KudoIkuru
en-aut-sei=Kudo
en-aut-mei=Ikuru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KotaniTohru
en-aut-sei=Kotani
en-aut-mei=Tohru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TakedaKazuhiko
en-aut-sei=Takeda
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YoshidaTakao
en-aut-sei=Yoshida
en-aut-mei=Takao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Research Center of Oncology, Ono Pharmaceutical, Co., Ltd.
kn-affil=

affil-num=4
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Research Center of Oncology, Ono Pharmaceutical, Co., Ltd.
kn-affil=

affil-num=6
en-affil=Research Center of Oncology, Ono Pharmaceutical, Co., Ltd.
kn-affil=

affil-num=7
en-affil=Research Center of Oncology, Ono Pharmaceutical, Co., Ltd.
kn-affil=

affil-num=8
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=1
article-no=
start-page=14928
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200910
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Dysfunction of CD8+PD-1+T cells in type 2 diabetes caused by the impairment of metabolism-immune axis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The metabolic changes and dysfunction in CD8+T cells may be involved in tumor progression and susceptibility to virus infection in type 2 diabetes (T2D). In C57BL/6JJcl mice fed with high fat-high sucrose chow (HFS), multifunctionality of CD8+splenic and tumor-infiltrating lymphocytes (TILs) was impaired and associated with enhanced tumor growth, which were inhibited by metformin. In CD8+splenic T cells from the HFS mice, glycolysis/basal respiration ratio was significantly reduced and reversed by metformin. In the patients with T2D (DM), multifunctionality of circulating CD8+PD-1+T cells stimulated with PMA/ionomycin as well as with HLA-A*24:02 CMV peptide was dampened, while metformin recovered multifunctionality. Both glycolysis and basal respiration were reduced in DM, and glycolysis was increased by metformin. The disturbance of the link between metabolism and immune function in CD8+PD-1+T cells in T2D was proved by recovery of antigen-specific and non-specific cytokine production via metformin-mediated increase in glycolytic activity.
en-copyright=
kn-copyright=

en-aut-name=NojimaIchiro
en-aut-sei=Nojima
en-aut-mei=Ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=EikawaShingo
en-aut-sei=Eikawa
en-aut-mei=Shingo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HadaYoshiko
en-aut-sei=Hada
en-aut-mei=Yoshiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KajitaniNobuo
en-aut-sei=Kajitani
en-aut-mei=Nobuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TeshigawaraSanae
en-aut-sei=Teshigawara
en-aut-mei=Sanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MiyamotoSatoshi
en-aut-sei=Miyamoto
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ToneAtsuhito
en-aut-sei=Tone
en-aut-mei=Atsuhito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=UchidaHaruhito A.
en-aut-sei=Uchida
en-aut-mei=Haruhito A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=ShikataKenichi
en-aut-sei=Shikata
en-aut-mei=Kenichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Hematology/Oncology, Hess Cancer Institute, Icahn School of Medicine At Mount Sinai
kn-affil=

affil-num=3
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Internal Medicine, Diabetes Center, Okayama City Hospital
kn-affil=

affil-num=6
en-affil=Diabetes Center, Okayama S
kn-affil=italama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci

affil-num=7
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Diabetes Center, Okayama Saiseikai General Hospital
kn-affil=

affil-num=9
en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=13
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Cytokines
kn-keyword=Cytokines
en-keyword=Diabetes
kn-keyword=Diabetes
en-keyword=Endocrine system and metabolic diseases
kn-keyword=Endocrine system and metabolic diseases
en-keyword=Immunology
kn-keyword=Immunology
en-keyword=Tumour immunology
kn-keyword=Tumour immunology
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=
article-no=
start-page=11934
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=2019815
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Berberine improved experimental chronic colitis by regulating interferon-gamma- and IL-17A-producing lamina propria CD4(+) T cells through AMPK activation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= The herbal medicine berberine (BBR) has been recently shown to be an AMP-activated protein kinase (AMPK) productive activator with various properties that induce anti-inflammatory responses. We investigated the effects of BBR on the mechanisms of mucosal CD4+T cell activation in vitro and on the inflammatory responses in T cell transfer mouse models of inflammatory bowel disease (IBD). We examined the favorable effects of BBR in vitro, using lamina propria (LP) CD4+ T cells in T cell transfer IBD models in which SCID mice had been injected with CD4+CD45RBhigh T cells. BBR suppressed the frequency of IFN-γ- and Il-17A-producing LP CD4+ T cells. This effect was found to be regulated by AMPK activation possibly induced by oxidative phosphorylation inhibition. We then examined the effects of BBR on the same IBD models in vivo. BBR-fed mice showed AMPK activation in the LPCD4+ T cells and an improvement of colitis. Our study newly showed that the BBR-induced AMPK activation of mucosal CD4+ T cells resulted in an improvement of IBD and underscored the importance of AMPK activity in colonic inflammation.
en-copyright=
kn-copyright=

en-aut-name=TakaharaMasahiro
en-aut-sei=Takahara
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TakakiAkinobu
en-aut-sei=Takaki
en-aut-mei=Akinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HiraokaSakiko
en-aut-sei=Hiraoka
en-aut-mei=Sakiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=AdachTakuya
en-aut-sei=Adach
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ShimomuraYasuyuki
en-aut-sei=Shimomura
en-aut-mei=Yasuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MatsushitaHiroshi
en-aut-sei=Matsushita
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=Nguyen Tien Thi Thuy
en-aut-sei=Nguyen Tien Thi Thuy
en-aut-mei=
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KoikeKazuko
en-aut-sei=Koike
en-aut-mei=Kazuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=IkedaAiri
en-aut-sei=Ikeda
en-aut-mei=Airi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=TakashimaShiho
en-aut-sei=Takashima
en-aut-mei=Shiho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=YamasakiYasushi
en-aut-sei=Yamasaki
en-aut-mei=Yasushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=InokuchiToshihiro
en-aut-sei=Inokuchi
en-aut-mei=Toshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=KinugasaHideaki
en-aut-sei=Kinugasa
en-aut-mei=Hideaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=SugiharaYusaku
en-aut-sei=Sugihara
en-aut-mei=Yusaku
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=HaradaKeita
en-aut-sei=Harada
en-aut-mei=Keita
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=EikawaShingo
en-aut-sei=Eikawa
en-aut-mei=Shingo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=MoritaHidetoshi
en-aut-sei=Morita
en-aut-mei=Hidetoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=OkadaHiroyuki
en-aut-sei=Okada
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

affil-num=1
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Department of Animal Applied Microbiology, Okayama University Graduate School of Environmental and Life Science
kn-affil=

affil-num=8
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=15
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=16
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=17
en-affil=Graduate School of Environmental and Life Science
kn-affil=

affil-num=18
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=19
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=25
cd-vols=
no-issue=
article-no=
start-page=154
end-page=164
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2017
dt-pub=20171016
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Attenuation of CD4+ CD25+ Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= CD4+CD25+ regulatory T cells (Treg), an essential subset for preventing autoimmune diseases, is implicated as a negative regulator in anti-tumor immunity. We found that metformin (Met) reduced tumor-infiltrating Treg (Ti-Treg), particularly the terminally-differentiated CD103+KLRG1+ population, and also decreased effector molecules such as CTLA4 and IL-10. Met inhibits the differentiation of na?ve CD4+ T cells into inducible Treg (iTreg) by reducing forkhead box P3 (Foxp3) protein, caused by mTORC1 activation that was determined by the elevation of phosphorylated S6 (pS6), a downstream molecule of mTORC1. Rapamycin and compound C, an inhibitor of AMP-activated protein kinase (AMPK) restored the iTreg generation, further indicating the involvement of mTORC1 and AMPK. The metabolic profile of iTreg, increased Glut1-expression, and reduced mitochondrial membrane-potential and ROS production of Ti-Treg aided in identifying enhanced glycolysis upon Met-treatment. The negative impact of Met on Ti-Treg may help generation of the sustained antitumor immunity.
en-copyright=
kn-copyright=

en-aut-name=KunisadaYuki
en-aut-sei=Kunisada
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=EikawaShingo
en-aut-sei=Eikawa
en-aut-mei=Shingo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=DomaeShohei
en-aut-sei=Domae
en-aut-mei=Shohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=UeharaTakenori
en-aut-sei=Uehara
en-aut-mei=Takenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HoriShohei
en-aut-sei=Hori
en-aut-mei=Shohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=FurusawaYukihiro
en-aut-sei=Furusawa
en-aut-mei=Yukihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HaseKoji
en-aut-sei=Hase
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SasakiAkira
en-aut-sei=Sasaki
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Laboratory of Immunology and Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo
kn-affil=

affil-num=7
en-affil=Division of Biochemistry, Keio University Graduate School of Pharmaceutical Science
kn-affil=

affil-num=8
en-affil=Division of Biochemistry, Keio University Graduate School of Pharmaceutical Science
kn-affil=

affil-num=9
en-affil=Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=10
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Glycolysis
kn-keyword=Glycolysis
en-keyword=Regulatory T cell (Treg)
kn-keyword=Regulatory T cell (Treg)
en-keyword=Tumor immunity
kn-keyword=Tumor immunity
en-keyword=Tumor microenvironment
kn-keyword=Tumor microenvironment
en-keyword=mTOR
kn-keyword=mTOR
END

start-ver=1.4
cd-journal=joma
no-vol=70
cd-vols=
no-issue=4
article-no=
start-page=327
end-page=330
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2016
dt-pub=201608
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Study about the Efficacy of Metformin to Immune Function in Cancer Patients
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A study to evaluate the effect of metformin on the immune system was commenced in July 2014. Metformin is one of the most commonly prescribed drugs for type 2 diabetes, and previous studies have reported that metformin has an anti-tumor effect. The aim of this study is to evaluate the efficacy of metformin on the immune system in human cancer patients in vivo. The primary outcome parameter will be the rate change in the population of CD8＋ T cells, which produce multiple cytokines. 
en-copyright=
kn-copyright=

en-aut-name=WatanabeMototsugu
en-aut-sei=Watanabe
en-aut-mei=Mototsugu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=EikawaShingo
en-aut-sei=Eikawa
en-aut-mei=Shingo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ShienTadahiko
en-aut-sei=Shien
en-aut-mei=Tadahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SohJunichi
en-aut-sei=Soh
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HinotsuShiro
en-aut-sei=Hinotsu
en-aut-mei=Shiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=DoiharaHiroyoshi
en-aut-sei=Doihara
en-aut-mei=Hiroyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=MiyoshiShinichiro
en-aut-sei=Miyoshi
en-aut-mei=Shinichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

affil-num=1
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=7
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=12
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=13
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=14
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=15
en-affil=Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=metformin
kn-keyword=metformin
en-keyword=CD8＋ T cells
kn-keyword=CD8＋ T cells
en-keyword=cancer immunology
kn-keyword=cancer immunology
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2015
dt-pub=201503
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Diabetes drug helps towards immunity against cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=鵜殿平一郎
kn-aut-sei=鵜殿
kn-aut-mei=平一郎
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Immunology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
END

start-ver=1.4
cd-journal=joma
no-vol=127
cd-vols=
no-issue=1
article-no=
start-page=73
end-page=74
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2015
dt-pub=20150401
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=The 9th Annual Meeting of the Biomedical Society for Stress Response
kn-title=第９回臨床ストレス応答学会大会開催報告
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=鵜殿平一郎
kn-aut-sei=鵜殿
kn-aut-mei=平一郎
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　免疫学
END

start-ver=1.4
cd-journal=joma
no-vol=42
cd-vols=
no-issue=19
article-no=
start-page=11903
end-page=11911
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20140927
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=HSP90α plays an important role in piRNA biogenesis and retrotransposon repression in mouse
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=HSP90, found in all kingdoms of life, is a major chaperone protein regulating many client proteins. We demonstrated that HSP90α, one of two paralogs duplicated in vertebrates, plays an important role in the biogenesis of fetal PIWI-interacting RNAs (piRNA), which act against the transposon activities, in mouse male germ cells. The knockout mutation of Hsp90α resulted in a large reduction in the expression of primary and secondary piRNAs and mislocalization of MIWI2, a PIWI homolog. Whereas the mutation in Fkbp6 encoding a co-chaperone reduced piRNAs of 28?32 nucleotides in length, the Hsp90α mutation reduced piRNAs of 24?32 nucleotides, suggesting the presence of both FKBP6-dependent and -independent actions of HSP90α. Although DNA methylation and mRNA levels of L1 retrotransposon were largely unchanged in the Hsp90α mutant testes, the L1-encoded protein was increased, suggesting the presence of post-transcriptional regulation. This study revealed the specialized function of the HSP90α isofom in the piRNA biogenesis and repression of retrotransposons during the development of male germ cells in mammals.
en-copyright=
kn-copyright=

en-aut-name=IchiyanagiTomoko
en-aut-sei=Ichiyanagi
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IchiyanagiKenji
en-aut-sei=Ichiyanagi
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OgawaAyako
en-aut-sei=Ogawa
en-aut-mei=Ayako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=Kuramochi-MiyagawaSatomi
en-aut-sei=Kuramochi-Miyagawa
en-aut-mei=Satomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NakanoToru
en-aut-sei=Nakano
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ChumaShinichiro
en-aut-sei=Chuma
en-aut-mei=Shinichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SasakiHiroyuki
en-aut-sei=Sasaki
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences

affil-num=2
en-affil=
kn-affil=Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University

affil-num=3
en-affil=
kn-affil=Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University

affil-num=4
en-affil=
kn-affil=Department of Pathology, Medical School and Graduate School of Frontier Biosciences, Osaka University

affil-num=5
en-affil=
kn-affil=Department of Pathology, Medical School and Graduate School of Frontier Biosciences, Osaka University

affil-num=6
en-affil=
kn-affil=Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University

affil-num=7
en-affil=
kn-affil=Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University

affil-num=8
en-affil=
kn-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
END

start-ver=1.4
cd-journal=joma
no-vol=125
cd-vols=
no-issue=1
article-no=
start-page=13
end-page=18
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20130401
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Cancer immunotherapy with blocking of immune checkpoints
kn-title=免疫チェックポイント制御とがん免疫治療
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=がんワクチンによる免疫治療では，如何にCD8T細胞を感作（プライミング）しその数を増やすか（免疫増強）という点に多大の努力が払われて来た．樹状細胞への抗原デリバリーと抗原プロセシング／提示，Toll様受容体などの刺激，即ち自然免疫系の活性化の併用などはそれに該当する．しかし十分に活性化されたＴ細胞をもってしても癌の拒絶は容易ではない．それには癌組織という特殊な環境が禍している．Ｔ細胞は癌塊内に入り込み莫大な数の癌細胞と遭遇する．癌組織内での繰り返す抗原認識の過程でＴ細胞は疲弊し，次第に本来あるべき機能を喪失していく．この疲弊（exhaustion）と呼ばれる現象は，Ｔ細胞に発現する複数の免疫抑制性分子―免疫チェックポイント分子―と腫瘍に発現するそのリガンドの結合によってもたらされる．代表的なチェックポイント分子の機能を抑制し，エフェクターＴ細胞が疲弊することなくその機能を長く維持できれば，これからのがん免疫治療に飛躍的な進展がみられるかもしれない．
en-copyright=
kn-copyright=

en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=鵜殿平一郎
kn-aut-sei=鵜殿
kn-aut-mei=平一郎
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　免疫学
en-keyword=がんワクチン
kn-keyword=がんワクチン
en-keyword=CTL
kn-keyword=CTL
en-keyword=免疫チェックポイント
kn-keyword=免疫チェックポイント
en-keyword=Ｔ細胞疲弊
kn-keyword=Ｔ細胞疲弊
END