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Article ; Online: Transcriptional and epigenetic basis of Treg cell development and function: its genetic anomalies or variations in autoimmune diseases.

Ohkura, Naganari / Sakaguchi, Shimon

2020 Volume 30, Issue 6, Page(s) 465–474

Abstract: Naturally arising regulatory ... ...

Abstract	Naturally arising regulatory CD4
MeSH term(s)	Animals ; Autoimmune Diseases/pathology ; CTLA-4 Antigen/genetics ; CTLA-4 Antigen/physiology ; DNA Methylation ; Epigenesis, Genetic ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/physiology ; Gene Expression Regulation ; Humans ; Interleukin-2 Receptor alpha Subunit/genetics ; Interleukin-2 Receptor alpha Subunit/physiology ; Polymorphism, Single Nucleotide ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/pathology
Chemical Substances	CTLA-4 Antigen ; CTLA4 protein, human ; FOXP3 protein, human ; Forkhead Transcription Factors ; IL2RA protein, human ; Interleukin-2 Receptor alpha Subunit
Language	English
Publishing date	2020-05-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1319303-x
ISSN	1748-7838 ; 1001-0602
ISSN (online)	1748-7838
ISSN	1001-0602
DOI	10.1038/s41422-020-0324-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 5283: Show issues

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Article ; Online: VIRTUS: a pipeline for comprehensive virus analysis from conventional RNA-seq data.

Yasumizu, Yoshiaki / Hara, Atsushi / Sakaguchi, Shimon / Ohkura, Naganari

Bioinformatics (Oxford, England)

2020 Volume 37, Issue 10, Page(s) 1465–1467

Abstract: Summary: The possibility that RNA transcripts from clinical samples contain plenty of virus RNAs has not been pursued actively so far. We here developed a new tool for analyzing virus-transcribed mRNAs, not virus copy numbers, in the data of bulk and ... ...

Abstract	Summary: The possibility that RNA transcripts from clinical samples contain plenty of virus RNAs has not been pursued actively so far. We here developed a new tool for analyzing virus-transcribed mRNAs, not virus copy numbers, in the data of bulk and single-cell RNA-sequencing of human cells. Our pipeline, named VIRTUS (VIRal Transcript Usage Sensor), was able to detect 762 viruses including herpesviruses, retroviruses and even SARS-CoV-2 (COVID-19), and quantify their transcripts in the sequence data. This tool thus enabled simultaneously detecting infected cells, the composition of multiple viruses within the cell, and the endogenous host-gene expression profile of the cell. This bioinformatics method would be instrumental in addressing the possible effects of covertly infecting viruses on certain diseases and developing new treatments to target such viruses. Availability and implementation: : VIRTUS is implemented using Common Workflow Language and Docker under a CC-NC license. VIRTUS is freely available at https://github.com/yyoshiaki/VIRTUS. Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	COVID-19 ; Humans ; RNA-Seq ; SARS-CoV-2 ; Sequence Analysis, RNA ; Software
Keywords	covid19
Language	English
Publishing date	2020-06-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btaa859
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Zs.A 2374: Show issues

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Article ; Online: Increased anti-oxidative action compensates for collagen tissue degeneration in vitiligo dermis.

Yokoi, Kazunori / Yasumizu, Yoshiaki / Ohkura, Naganari / Shinzawa, Koei / Okuzaki, Daisuke / Shimoda, Nene / Ando, Hideya / Yamada, Nanako / Fujimoto, Manabu / Tanemura, Atsushi

Pigment cell & melanoma research

2023 Volume 36, Issue 5, Page(s) 355–364

Abstract: Vitiligo is a common depigmentation disorder characterized by the selective loss of melanocytes. In our daily clinic experience, we noticed that the skin tightness of hypopigmented lesions would be more evident in comparison to that of uninvolved ... ...

Abstract	Vitiligo is a common depigmentation disorder characterized by the selective loss of melanocytes. In our daily clinic experience, we noticed that the skin tightness of hypopigmented lesions would be more evident in comparison to that of uninvolved perilesional skin in vitiligo patients. Therefore, we hypothesized that collagen homeostasis might be maintained in vitiligo lesions, irrespective of the substantial excessive oxidative stress that occurs in association with the disease. We found that the expression levels of collagen-related genes and anti-oxidative enzymes were upregulated in vitiligo-derived fibroblasts. Abundant collagenous fibers were observed in the papillary dermis of vitiligo lesions in comparison to uninvolved perilesional skin by electron microscopy. The production of matrix metalloproteinases that degraded collagen fibers was suppressed. The deposition of acrolein adduct protein, which is a product of oxidative stress, was significantly reduced in vitiligo dermis and fibroblasts. As part of the mechanism, we found upregulation of the NRF2 signaling pathway activity, which is an important defense system against oxidative stress. Taken together, we demonstrated that the anti-oxidative action and collagen production were upregulated and that the collagen degeneration was attenuated in vitiligo dermis. These new findings may provide important clues for the maintenance of antioxidant ability in vitiligo lesions.
MeSH term(s)	Humans ; Vitiligo/pathology ; Hypopigmentation/metabolism ; Skin/pathology ; Melanocytes/metabolism ; Oxidative Stress ; Dermis/pathology ; Collagen/metabolism
Chemical Substances	Collagen (9007-34-5)
Language	English
Publishing date	2023-05-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2409570-9
ISSN	1755-148X ; 1600-0749 ; 0893-5785 ; 1755-1471
ISSN (online)	1755-148X ; 1600-0749
ISSN	0893-5785 ; 1755-1471
DOI	10.1111/pcmr.13094
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Zs.A 2444: Show issues

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Article ; Online: Downregulation of TCF7 and LEF1 is a key determinant of tumor-infiltrating regulatory T-cell function.

Kidani, Yujiro / Kitagawa, Yohko / Hagiwara, Masaki / Kawashima, Atsunari / Kanazawa, Takayuki / Wada, Hisashi / Uemura, Motohide / Nonomura, Norio / Motooka, Daisuke / Nakamura, Shota / Ohkura, Naganari / Sakaguchi, Shimon

International immunology

2024 Volume 36, Issue 4, Page(s) 167–182

Abstract: Forkhead box P3 (Foxp3)-expressing regulatory T (Treg) cells play essential roles in immune homeostasis but also contribute to establish a favorable environment for tumor growth by suppressing anti-tumor immune responses. It is thus necessary to ... ...

Abstract	Forkhead box P3 (Foxp3)-expressing regulatory T (Treg) cells play essential roles in immune homeostasis but also contribute to establish a favorable environment for tumor growth by suppressing anti-tumor immune responses. It is thus necessary to specifically target tumor-infiltrating Treg cells to minimize effects on immune homeostasis in cancer immunotherapy. However, molecular features that distinguish tumor-infiltrating Treg cells from those in secondary lymphoid organs remain unknown. Here we characterize distinct features of tumor-infiltrating Treg cells by global analyses of the transcriptome and chromatin landscape. They exhibited activated phenotypes with enhanced Foxp3-dependent transcriptional regulation, yet being distinct from activated Treg cells in secondary lymphoid organs. Such differences may be attributed to the extensive clonal expansion of tumor-infiltrating Treg cells. Moreover, we found that TCF7 and LEF1 were specifically downregulated in tumor-infiltrating Treg cells both in mice and humans. These factors and Foxp3 co-occupied Treg suppressive function-related gene loci in secondary lymphoid organ Treg cells, whereas the absence of TCF7 and LEF1 accompanied altered gene expression and chromatin status at these gene loci in tumor-infiltrating Treg cells. Functionally, overexpression of TCF7 and LEF1 in Treg cells inhibited the enhancement of Treg suppressive function upon activation. Our results thus show the downregulation of TCF7 and LEF1 as markers of highly suppressive Treg cells in tumors and suggest that their absence controls the augmentation of Treg suppressive function in tumors. These molecules may be potential targets for novel cancer immunotherapy with minimum effects on immune homeostasis.
MeSH term(s)	Humans ; Animals ; Mice ; T-Lymphocytes, Regulatory ; Down-Regulation ; Forkhead Transcription Factors/metabolism ; Neoplasms ; Chromatin/metabolism ; T Cell Transcription Factor 1/genetics ; T Cell Transcription Factor 1/metabolism ; Lymphoid Enhancer-Binding Factor 1/genetics ; Lymphoid Enhancer-Binding Factor 1/metabolism
Chemical Substances	Forkhead Transcription Factors ; Chromatin ; TCF7 protein, human ; T Cell Transcription Factor 1 ; LEF1 protein, human ; Lymphoid Enhancer-Binding Factor 1
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Journal Article
ZDB-ID	1013745-2
ISSN	1460-2377 ; 0953-8178
ISSN (online)	1460-2377
ISSN	0953-8178
DOI	10.1093/intimm/dxad053
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Zs.A 2619: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Single-cell transcriptome landscape of circulating CD4

Yasumizu, Yoshiaki / Takeuchi, Daiki / Morimoto, Reo / Takeshima, Yusuke / Okuno, Tatsusada / Kinoshita, Makoto / Morita, Takayoshi / Kato, Yasuhiro / Wang, Min / Motooka, Daisuke / Okuzaki, Daisuke / Nakamura, Yamami / Mikami, Norihisa / Arai, Masaya / Zhang, Xuan / Kumanogoh, Atsushi / Mochizuki, Hideki / Ohkura, Naganari / Sakaguchi, Shimon

Cell genomics

2024 Volume 4, Issue 2, Page(s) 100473

Abstract: ... ...

Abstract	CD4
MeSH term(s)	Humans ; Transcriptome/genetics ; T-Lymphocytes ; Autoimmune Diseases/genetics ; CD4-Positive T-Lymphocytes
Language	English
Publishing date	2024-01-03
Publishing country	United States
Document type	Meta-Analysis ; Journal Article
ISSN	2666-979X
ISSN (online)	2666-979X
DOI	10.1016/j.xgen.2023.100473
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Article ; Online: VIRTUS: a pipeline for comprehensive virus analysis from conventional RNA-seq data

Yasumizu, Yoshiaki / Hara, Atsushi / Sakaguchi, Shimon / Ohkura, Naganari

bioRxiv

Abstract: The possibility that RNA transcripts from clinical samples contain plenty of virus RNAs has not been pursued actively so far. We here developed a new tool for analyzing virus-transcribed mRNAs, not virus copy numbers, in the data of conventional and ... ...

Abstract	The possibility that RNA transcripts from clinical samples contain plenty of virus RNAs has not been pursued actively so far. We here developed a new tool for analyzing virus-transcribed mRNAs, not virus copy numbers, in the data of conventional and single-cell RNA-sequencing of human cells. Our pipeline, named VIRTUS (VIRal Transcript Usage Sensor), was able to detect 763 viruses including herpesviruses, retroviruses, and even SARS-CoV-2 (COVID-19), and quantify their transcripts in the sequence data. This tool thus enabled simultaneously detecting infected cells, the composition of multiple viruses within the cell, and the endogenous host gene expression profile of the cell. This bioinformatics method would be instrumental in addressing the possible effects of covertly infecting viruses on certain diseases and developing new treatments to target such viruses. Availability and implementation VIRTUS is implemented using Common Workflow Language and Docker under a CC-NC license. VIRTUS is freely available at https://github.com/yyoshiaki/VIRTUS. Supplementary information Supplementary data are available at Bioinformatics online.
Keywords	covid19
Publisher	BioRxiv; WHO
Document type	Article ; Online
DOI	10.1101/2020.05.08.085308
Database	COVID19

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Article ; Online: VIRTUS: a pipeline for comprehensive virus analysis from conventional RNA-seq data

Yasumizu, Yoshiaki / Hara, Atsushi / Sakaguchi, Shimon / Ohkura, Naganari

bioRxiv

Abstract: The possibility that RNA transcripts from clinical samples contain a plenty of virus RNAs has not been pursued actively so far. We here developed a new tool for analyzing virus-transcribed mRNAs, not virus copy numbers, in the data of conventional and ... ...

Abstract	The possibility that RNA transcripts from clinical samples contain a plenty of virus RNAs has not been pursued actively so far. We here developed a new tool for analyzing virus-transcribed mRNAs, not virus copy numbers, in the data of conventional and single-cell RNA-sequencing of human cells. Our pipeline, named VIRTUS (VIRal Transcript Usage Sensor), was able to detect 763 viruses including herpesviruses, retroviruses, and even SARS-CoV-2 (COVID-19), and quantify their transcripts in the sequence data. This tool thus enabled simultaneously detecting infected cells, the composition of multiple viruses within the cell, and the endogenous host gene expression profile of the cell. This bioinformatics method would be instrumental in addressing possible effects of covertly infecting viruses on certain diseases and developing new treatments to target１ such viruses.
Keywords	covid19
Language	English
Publishing date	2020-05-09
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2020.05.08.085308
Database	COVID19

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Article ; Online: VIRTUS

Yasumizu, Yoshiaki / Hara, Atsushi / Sakaguchi, Shimon / Ohkura, Naganari

Bioinformatics ; ISSN 1367-4803 1460-2059

a pipeline for comprehensive virus analysis from conventional RNA-seq data

2020

Abstract: Abstract The possibility that RNA transcripts from clinical samples contain plenty of virus RNAs has not been pursued actively so far. We here developed a new tool for analyzing virus-transcribed mRNAs, not virus copy numbers, in the data of bulk and ... ...

Abstract	Abstract The possibility that RNA transcripts from clinical samples contain plenty of virus RNAs has not been pursued actively so far. We here developed a new tool for analyzing virus-transcribed mRNAs, not virus copy numbers, in the data of bulk and single-cell RNA-sequencing of human cells. Our pipeline, named VIRTUS (VIRal Transcript Usage Sensor), was able to detect 762 viruses including herpesviruses, retroviruses, and even SARS-CoV-2 (COVID-19), and quantify their transcripts in the sequence data. This tool thus enabled simultaneously detecting infected cells, the composition of multiple viruses within the cell, and the endogenous host gene expression profile of the cell. This bioinformatics method would be instrumental in addressing the possible effects of covertly infecting viruses on certain diseases and developing new treatments to target such viruses. Availability VIRTUS is implemented using Common Workflow Language and Docker under a CC-NC license. VIRTUS is freely available at https://github.com/yyoshiaki/VIRTUS. Supplementary information Supplementary data are available at Bioinformatics online.
Keywords	Statistics and Probability ; Computational Theory and Mathematics ; Biochemistry ; Molecular Biology ; Computational Mathematics ; Computer Science Applications ; covid19
Language	English
Publisher	Oxford University Press (OUP)
Publishing country	uk
Document type	Article ; Online
DOI	10.1093/bioinformatics/btaa859
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Regulatory T Cells and Human Disease.

Sakaguchi, Shimon / Mikami, Norihisa / Wing, James B / Tanaka, Atsushi / Ichiyama, Kenji / Ohkura, Naganari

Annual review of immunology

2020 Volume 38, Page(s) 541–566

Abstract: Naturally occurring ... ...

Abstract	Naturally occurring CD4
MeSH term(s)	Animals ; Autoimmune Diseases/etiology ; Autoimmune Diseases/metabolism ; Autoimmune Diseases/pathology ; Autoimmune Diseases/therapy ; Autoimmunity ; Biomarkers ; Disease Management ; Disease Susceptibility ; Humans ; Lymphocyte Activation/immunology ; Molecular Targeted Therapy ; Self Tolerance/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism
Chemical Substances	Biomarkers
Language	English
Publishing date	2020-02-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	604953-9
ISSN	1545-3278 ; 0732-0582
ISSN (online)	1545-3278
ISSN	0732-0582
DOI	10.1146/annurev-immunol-042718-041717
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Article ; Online: Epigenetic conversion of conventional T cells into regulatory T cells by CD28 signal deprivation.

Mikami, Norihisa / Kawakami, Ryoji / Chen, Kelvin Y / Sugimoto, Atsushi / Ohkura, Naganari / Sakaguchi, Shimon

Proceedings of the National Academy of Sciences of the United States of America

2020 Volume 117, Issue 22, Page(s) 12258–12268

Abstract: Foxp3-expressing regulatory T cells (Tregs) can be generated in vitro by antigenic stimulation of conventional T cells (Tconvs) in the presence of TGF-β and IL-2. However, unlike ... ...

Abstract	Foxp3-expressing regulatory T cells (Tregs) can be generated in vitro by antigenic stimulation of conventional T cells (Tconvs) in the presence of TGF-β and IL-2. However, unlike Foxp3
MeSH term(s)	Animals ; CD28 Antigens/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cell Differentiation ; Cytokines/metabolism ; DNA Methylation ; Epigenesis, Genetic ; Female ; Forkhead Transcription Factors/physiology ; Gene Expression Regulation ; Interleukin-6/metabolism ; Male ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Signal Transduction ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Transforming Growth Factor beta/metabolism
Chemical Substances	CD28 Antigens ; Cytokines ; Forkhead Transcription Factors ; Foxp3 protein, mouse ; Interleukin-6 ; Transforming Growth Factor beta ; interleukin-6, mouse
Language	English
Publishing date	2020-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1922600117
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