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Article ; Online: Antimalarial ceramicines Q-T from Chisocheton ceramicus.

Nugroho, Alfarius Eko / Wong, Chin Piow / Hirasawa, Yusuke / Kaneda, Toshio / Tougan, Takahiro / Horii, Toshihiro / Hadi, A Hamid A / Morita, Hiroshi

Journal of natural medicines

2023 Volume 77, Issue 3, Page(s) 596–603

Abstract: ... T (1-4) were isolated from the barks of C. ceramicus, and their structures were determined ...

Abstract	Ceramicines are a series of limonoids that were isolated from the bark of Malaysian Chisocheton ceramicus (Meliaceae) and were known to show various biological activity. Four new limonoids, ceramicines Q-T (1-4) were isolated from the barks of C. ceramicus, and their structures were determined on the basis of the 1D and 2D NMR analyses in combination with calculated
MeSH term(s)	Antimalarials/pharmacology ; Limonins/chemistry ; Magnetic Resonance Spectroscopy ; Plasmodium falciparum ; Meliaceae/chemistry
Chemical Substances	Antimalarials ; Limonins
Language	English
Publishing date	2023-05-10
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2227540-X
ISSN	1861-0293 ; 1340-3443
ISSN (online)	1861-0293
ISSN	1340-3443
DOI	10.1007/s11418-023-01706-w
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Article ; Online: CD4-positive extranodal NK/T-cell lymphoma with T-cell receptor αβ phenotype.

Hisamoto, Teruyoshi / Miyagaki, Tomomitsu / Boki, Hikari / Takahashi-Shishido, Naomi / Chiba, Akira / Yasunaga, Megumi / Mizuno, Hideki / Shimura, Arika / Morita, Ken / Sato, Shinichi

The Journal of dermatology

2023 Volume 50, Issue 10, Page(s) e337–e339

MeSH term(s)	Humans ; Lymphoma, Extranodal NK-T-Cell/diagnosis ; Lymphoma, Extranodal NK-T-Cell/pathology ; Lymphoma, T-Cell, Peripheral/pathology ; Phenotype ; Receptors, Antigen, T-Cell/genetics
Chemical Substances	Receptors, Antigen, T-Cell
Language	English
Publishing date	2023-05-19
Publishing country	England
Document type	Case Reports ; Letter
ZDB-ID	800103-0
ISSN	1346-8138 ; 0385-2407
ISSN (online)	1346-8138
ISSN	0385-2407
DOI	10.1111/1346-8138.16844
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Article ; Online: Allosteric inhibition of the T cell receptor by a designed membrane ligand.

Ye, Yujie / Morita, Shumpei / Chang, Justin J / Buckley, Patrick M / Wilhelm, Kiera B / DiMaio, Daniel / Groves, Jay T / Barrera, Francisco N

eLife

2023 Volume 12

Abstract: The T cell receptor (TCR) is a complex molecular machine that directs the activation of T ... peptide caused a reduction of Lck phosphorylation of TCR at the CD3ζ subunit in T cells. As a result ...

Abstract	The T cell receptor (TCR) is a complex molecular machine that directs the activation of T cells, allowing the immune system to fight pathogens and cancer cells. Despite decades of investigation, the molecular mechanism of TCR activation is still controversial. One of the leading activation hypotheses is the allosteric model. This model posits that binding of pMHC at the extracellular domain triggers a dynamic change in the transmembrane (TM) domain of the TCR subunits, which leads to signaling at the cytoplasmic side. We sought to test this hypothesis by creating a TM ligand for TCR. Previously we described a method to create a soluble peptide capable of inserting into membranes and binding to the TM domain of the receptor tyrosine kinase EphA2 (Alves et al., eLife, 2018). Here, we show that the approach is generalizable to complex membrane receptors, by designing a TM ligand for TCR. We observed that the designed peptide caused a reduction of Lck phosphorylation of TCR at the CD3ζ subunit in T cells. As a result, in the presence of this peptide inhibitor of TCR (PITCR), the proximal signaling cascade downstream of TCR activation was significantly dampened. Co-localization and co-immunoprecipitation in diisobutylene maleic acid (DIBMA) native nanodiscs confirmed that PITCR was able to bind to the TCR. AlphaFold-Multimer predicted that PITCR binds to the TM region of TCR, where it interacts with the two CD3ζ subunits. Our results additionally indicate that PITCR disrupts the allosteric changes in the compactness of the TM bundle that occur upon TCR activation, lending support to the allosteric TCR activation model. The TCR inhibition achieved by PITCR might be useful to treat inflammatory and autoimmune diseases and to prevent organ transplant rejection, as in these conditions aberrant activation of TCR contributes to disease.
MeSH term(s)	Ligands ; Receptors, Antigen, T-Cell/metabolism ; T-Lymphocytes ; Phosphorylation ; Peptides/pharmacology ; Peptides/metabolism
Chemical Substances	Ligands ; Receptors, Antigen, T-Cell ; Peptides
Language	English
Publishing date	2023-10-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.82861
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Article ; Online: Optical vortex induced spatio-temporally modulated superconductivity in a high-T

Toda, Yasunori / Tsuchiya, Satoshi / Yamane, Keisaku / Morita, Ryuji / Oda, Migaku / Kurosawa, Tohru / Mertelj, Tomaz / Mihailovic, Dragan

Optics express

2023 Volume 31, Issue 11, Page(s) 17537–17546

Abstract: We report an experimental approach to produce spatially localized photoinduced superconducting state in a cuprate superconductor using optical vortices with ultrafast pulses. The measurements were carried out using coaxially aligned three-pulse time- ... ...

Abstract	We report an experimental approach to produce spatially localized photoinduced superconducting state in a cuprate superconductor using optical vortices with ultrafast pulses. The measurements were carried out using coaxially aligned three-pulse time-resolved spectroscopy, in which an intense vortex pulse was used for coherent quenching of superconductivity and the resulting spatially modulated metastable states were analyzed by the pump-probe spectroscopy. The transient response after quenching shows a spatially localized superconducting state that remains unquenched at the dark core of the vortex beam for a few picoseconds. Because the quenching is instantaneously driven by photoexcited quasiparticles, the vortex beam profile can be transferred directly to the electron system. By using the optical vortex-induced superconductor, we demonstrate spatially resolved imaging of the superconducting response and show that the spatial resolution can be improved using the same principle as that of super-resolution microscopy for fluorescent molecules. The demonstration of spatially controlled photoinduced superconductivity is significant for establishing a new method for exploring novel photoinduced phenomena and applications in ultrafast optical devices.
Language	English
Publishing date	2023-06-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1491859-6
ISSN	1094-4087 ; 1094-4087
ISSN (online)	1094-4087
ISSN	1094-4087
DOI	10.1364/OE.487041
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Article ; Online: CD8+ Regulatory T Cells Induced by Lipopolysaccharide Improve Mouse Endotoxin Shock.

Morita, Nanaka / Hoshi, Masato / Tezuka, Hiroyuki / Ando, Tatsuya / Yoshida, Sayaka / Sato, Fumiaki / Yokoi, Hiroyuki / Ito, Hiroyasu / Saito, Kuniaki

ImmunoHorizons

2023 Volume 7, Issue 5, Page(s) 353–363

Abstract: ... Therefore, immunotherapy may be effective in treating sepsis. Although CD8+ regulatory T cells (Tregs) are known to have ...

Abstract	Sepsis is a systemic inflammatory disease caused by a bacterial infection that leads to severe mortality, especially in elderly patients, because of an excessive immune response and impaired regulatory functions. Antibiotic treatment is widely accepted as the first-line therapy for sepsis; however, its excessive use has led to the emergence of multidrug-resistant bacteria in patients with sepsis. Therefore, immunotherapy may be effective in treating sepsis. Although CD8+ regulatory T cells (Tregs) are known to have immunomodulatory effects in various inflammatory diseases, their role during sepsis remains unclear. In this study, we investigated the role of CD8+ Tregs in an LPS-induced endotoxic shock model in young (8-12 wk old) and aged (18-20 mo old) mice. The adoptive transfer of CD8+ Tregs into LPS-treated young mice improved the survival rate of LPS-induced endotoxic shock. Moreover, the number of CD8+ Tregs in LPS-treated young mice increased through the induction of IL-15 produced by CD11c+ cells. In contrast, LPS-treated aged mice showed a reduced induction of CD8+ Tregs owing to the limited production of IL-15. Furthermore, CD8+ Tregs induced by treatment with the rIL-15/IL-15Rα complex prevented LPS-induced body wight loss and tissue injury in aged mice. In this study, to our knowledge, the induction of CD8+ Tregs as novel immunotherapy or adjuvant therapy for endotoxic shock might reduce the uncontrolled immune response and ultimately improve the outcomes of endotoxic shock.
MeSH term(s)	Mice ; Animals ; Shock, Septic/therapy ; Lipopolysaccharides ; T-Lymphocytes, Regulatory ; Interleukin-15 ; Sepsis ; CD8-Positive T-Lymphocytes
Chemical Substances	Lipopolysaccharides ; Interleukin-15
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2573-7732
ISSN (online)	2573-7732
DOI	10.4049/immunohorizons.2200074
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Article ; Online: Hemoglobin-platelet index as a prognostic factor in patients with peripheral T-cell lymphoma.

Yagi, Yu / Kanemasa, Yusuke / Sasaki, Yuki / Okumura, Shunichi / Watanabe, Takako / Ishimine, Kento / Hayashi, Yudai / Mino, Mano / Ohigashi, An / Morita, Yuka / Tamura, Taichi / Nakamura, Shohei / Okuya, Toshihiro / Shimoyama, Tatsu

EJHaem

2023 Volume 4, Issue 3, Page(s) 656–666

Abstract: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with a poor ...

Abstract	Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with a poor prognosis. The International Prognostic Index (IPI) and the Prognostic Index for PTCL-unspecified (PIT) is used to predict the prognosis of PTCL. The hemoglobin-platelet index (HPI), based on anemia and thrombocytopenia status, is associated with the prognosis of diffuse large B-cell lymphoma. However, its significance in terms of predicting the prognosis of PTCL has not been fully investigated. We herein retrospectively analyzed 100 patients with newly diagnosed PTCL in our department. At a median follow-up of 3.2 years, the median progression-free survival (PFS) and overall survival (OS) was 0.72 (95% confidence interval [CI]: 0.56-1.2) years and 2.0 (95% CI: 1.5-4.7) years, respectively. Multivariate analysis revealed that elevated lactic dehydrogenase (LDH) and hypoalbuminemia were independent adverse variables for PFS. The HPI showed significant predictive value for both PFS and OS. As a new prognostic model comprising the HPI, LDH, and albumin, the LA-HPI allowed the stratification of patients into four distinct risk subgroups: low risk (zero risk factors), low-intermediate risk (one risk factors), high-intermediate risk (two or three risk factors), or high risk (four risk factors). The PFS and OS differed significantly among the patients by the LA-HPI score. The LA-HPI demonstrated better predictive performance compared to the IPI, PIT, and HPI. Our data demonstrated the prognostic utility of the HPI in patients with PTCL. The LA-HPI, incorporating four readily obtainable parameters, exhibited superior performance compared to traditional indices.
Language	English
Publishing date	2023-05-26
Publishing country	United States
Document type	Journal Article
ISSN	2688-6146
ISSN (online)	2688-6146
DOI	10.1002/jha2.727
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Article ; Online: Fatty Acids Play a Critical Role in Mitochondrial Oxidative Phosphorylation in Effector T Cells in Graft-versus-Host Disease.

Nakano, Hirofumi / Sato, Kazuya / Izawa, Junko / Takayama, Norihito / Hayakawa, Hiroko / Ikeda, Takashi / Kawaguchi, Shin-Ichiro / Mashima, Kiyomi / Umino, Kento / Morita, Kaoru / Ito, Ryoji / Ohno, Nobuhiko / Tominaga, Kaoru / Endo, Hitoshi / Kanda, Yoshinobu

ImmunoHorizons

2024 Volume 8, Issue 3, Page(s) 228–241

Abstract: Although the role of aerobic glycolysis in activated T cells has been well characterized ... whether and how fatty acids (FAs) contribute to donor T cell function in allogeneic ... that exogenous FAs serve as a crucial source of mitochondrial respiration in donor T cells in humans ...

Abstract	Although the role of aerobic glycolysis in activated T cells has been well characterized, whether and how fatty acids (FAs) contribute to donor T cell function in allogeneic hematopoietic stem cell transplantation is unclear. Using xenogeneic graft-versus-host disease (GVHD) models, this study demonstrated that exogenous FAs serve as a crucial source of mitochondrial respiration in donor T cells in humans. By comparing human T cells isolated from wild-type NOD/Shi-scid-IL2rγnull (NOG) mice with those from MHC class I/II-deficient NOG mice, we found that donor T cells increased extracellular FA uptake, the extent of which correlates with their proliferation, and continued to increase FA uptake during effector differentiation. Gene expression analysis showed the upregulation of a wide range of lipid metabolism-related genes, including lipid hydrolysis, mitochondrial FA transport, and FA oxidation. Extracellular flux analysis demonstrated that mitochondrial FA transport was required to fully achieve the mitochondrial maximal respiration rate and spare respiratory capacity, whereas the substantial disruption of glucose supply by either glucose deprivation or mitochondrial pyruvate transport blockade did not impair oxidative phosphorylation. Taken together, FA-driven mitochondrial respiration is a hallmark that differentiates TCR-dependent T cell activation from TCR-independent immune response after hematopoietic stem cell transplant.
MeSH term(s)	Humans ; Animals ; Mice ; Mice, Inbred NOD ; Oxidative Phosphorylation ; T-Lymphocytes ; Graft vs Host Disease ; Fatty Acids ; Glucose ; Mice, SCID ; Receptors, Antigen, T-Cell
Chemical Substances	Fatty Acids ; Glucose (IY9XDZ35W2) ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ISSN	2573-7732
ISSN (online)	2573-7732
DOI	10.4049/immunohorizons.2300115
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Article ; Online: Sema6D forward signaling impairs T cell activation and proliferation in head and neck cancer.

Hirai, Takashi / Naito, Yujiro / Koyama, Shohei / Nakanishi, Yoshimitsu / Masuhiro, Kentaro / Izumi, Mayuko / Kuge, Tomoki / Naito, Maiko / Mizuno, Yumiko / Yamaguchi, Yuta / Kang, Sujin / Yaga, Moto / Futami, Yu / Nojima, Satoshi / Nishide, Masayuki / Morita, Takayoshi / Kato, Yasuhiro / Tsuda, Takeshi / Takemoto, Norihiko /

Kinugasa-Katayama, Yumi / Aoshi, Taiki / Villa, Jordan Kelly / Yamashita, Kazuo / Enokida, Tomohiro / Hoshi, Yuta / Matsuura, Kazuto / Tahara, Makoto / Takamatsu, Hyota / Takeda, Yoshito / Inohara, Hidenori / Kumanogoh, Atsushi

JCI insight

2024 Volume 9, Issue 3

Abstract: ... ICIs. T cell infiltration and activation status in the tumor microenvironment greatly affects ... and activation of tumor-specific CD8+ T cells in murine oral tumors. Sema6D expressed ... by nonhematopoietic cells was responsible for this phenotype. Plexin-A4, a receptor for Sema6D, inhibited T cell ...

Abstract	Immune checkpoint inhibitors (ICIs) are indicated for a diverse range of cancer types, and characterizing the tumor immune microenvironment is critical for optimizing therapeutic strategies, including ICIs. T cell infiltration and activation status in the tumor microenvironment greatly affects the efficacy of ICIs. Here, we show that semaphorin 6D (Sema6D) forward signaling, which is reportedly involved in coordinating the orientation of cell development and migration as a guidance factor, impaired the infiltration and activation of tumor-specific CD8+ T cells in murine oral tumors. Sema6D expressed by nonhematopoietic cells was responsible for this phenotype. Plexin-A4, a receptor for Sema6D, inhibited T cell infiltration and partially suppressed CD8+ T cell activation and proliferation induced by Sema6D stimulation. Moreover, mouse oral tumors, which are resistant to PD-1-blocking treatment in wild-type mice, showed a response to the treatment in Sema6d-KO mice. Finally, analyses of public data sets of human head and neck squamous cell carcinoma, pan-cancer cohorts, and a retrospective cohort study showed that SEMA6D was mainly expressed by nonhematopoietic cells such as cancer cells, and SEMA6D expression was significantly negatively correlated with CD8A, PDCD1, IFNG, and GZMB expression. Thus, targeting Sema6D forward signaling is a promising option for increasing ICI efficacy.
MeSH term(s)	Animals ; Humans ; Mice ; Cell Proliferation ; Head and Neck Neoplasms/genetics ; Mouth Neoplasms ; Retrospective Studies ; Squamous Cell Carcinoma of Head and Neck/genetics ; Tumor Microenvironment
Chemical Substances	Sema6d protein, mouse
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.166349
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Article ; Online: Saturation Recovery Myocardial T

Morita, Kosuke / Oda, Seitaro / Utsunomiya, Daisuke / Nakaura, Takeshi / Matsubara, Takatoshi / Goto, Makoto / Okuaki, Tomoyuki / Yuki, Hideaki / Nagayama, Yasunori / Kidoh, Masafumi / Hirata, Kenichiro / Iyama, Yuij / Taguchi, Narumi / Hatemura, Masahiro / Hashida, Masahiro / Yamashita, Yasuyuki

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine

2018 Volume 17, Issue 1, Page(s) 35–41

Abstract: ... SR) myocardial T: Materials and methods: Phantom and in vivo studies were performed ... with a clinical 3T MR scanner. Accuracy and reproducibility of the SR T: Results: The phantom study revealed ... significant differences in the mean T: Conclusion: SR T ...

Abstract	Purpose: To evaluate the effect of a composite radiofrequency (RF) pulse on saturation recovery (SR) myocardial T Materials and methods: Phantom and in vivo studies were performed with a clinical 3T MR scanner. Accuracy and reproducibility of the SR T Results: The phantom study revealed significant differences in the mean T Conclusion: SR T
MeSH term(s)	Adult ; Female ; Humans ; Image Interpretation, Computer-Assisted/methods ; Magnetic Resonance Imaging/methods ; Male ; Middle Aged ; Myocardium/pathology ; Phantoms, Imaging ; Radio Waves ; Reproducibility of Results
Language	English
Publishing date	2018-01-10
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2217833-8
ISSN	1880-2206 ; 1347-3182
ISSN (online)	1880-2206
ISSN	1347-3182
DOI	10.2463/mrms.mp.2016-0092
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Article ; Online: IL-25 enhances T

Suto, Hajime / Nambu, Aya / Morita, Hideaki / Yamaguchi, Sachiko / Numata, Takafumi / Yoshizaki, Takamichi / Shimura, Eri / Arae, Ken / Asada, Yousuke / Motomura, Kenichiro / Kaneko, Mari / Abe, Takaya / Matsuda, Akira / Iwakura, Yoichiro / Okumura, Ko / Saito, Hirohisa / Matsumoto, Kenji / Sudo, Katsuko / Nakae, Susumu

The Journal of allergy and clinical immunology

2018 Volume 142, Issue 5, Page(s) 1500–1509.e10

Abstract: Background: In addition to thymic stromal lymphopoietin and IL-33, IL-25 is known to induce T ... Skin dendritic cell (DC) migration, hapten-specific T: Results: In contrast to thymic stromal lymphopoietin ... we found that IL-25 was not essential for skin DC migration or hapten-specific T: Conclusion ...

Abstract	Background: In addition to thymic stromal lymphopoietin and IL-33, IL-25 is known to induce T Objective: We investigated the contribution of IL-25 to CHS using Il25 Methods: CHS was evaluated by means of measurement of ear skin thickness in mice after fluorescein isothiocyanate painting. Skin dendritic cell (DC) migration, hapten-specific T Results: In contrast to thymic stromal lymphopoietin, we found that IL-25 was not essential for skin DC migration or hapten-specific T Conclusion: Our results identify a novel IL-25 inflammatory pathway involved in induction of T
MeSH term(s)	Animals ; Cytokines/genetics ; Cytokines/immunology ; DNA-Binding Proteins/genetics ; Dermatitis, Allergic Contact/immunology ; Female ; Male ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics ; STAT6 Transcription Factor/genetics ; Th17 Cells/immunology
Chemical Substances	Cytokines ; DNA-Binding Proteins ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; Rag2 protein, mouse ; Rorc protein, mouse ; STAT6 Transcription Factor ; Stat6 protein, mouse ; thymic stromal lymphopoietin (GT0IL38SP4)
Language	English
Publishing date	2018-03-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2017.12.1007
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