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Article ; Online: SOCS3 deletion in effector T cells confers an anti-tumorigenic role of IL-6 to the pro-tumorigenic cytokine.

Mise-Omata, Setsuko / Ando, Makoto / Srirat, Tanakorn / Nakagawara, Kensuke / Hayakawa, Taeko / Iizuka-Koga, Mana / Nishimasu, Hiroshi / Nureki, Osamu / Ito, Minako / Yoshimura, Akihiko

Cell reports

2023 Volume 42, Issue 8, Page(s) 112940

Abstract: Interleukin (IL)-6 is abundantly expressed in the tumor microenvironment and is associated with poor patient outcomes. Here, we demonstrate that the deletion of the suppressor of cytokine signaling 3 (SOCS3) in T cells potentiates anti-tumor immune ... ...

Abstract	Interleukin (IL)-6 is abundantly expressed in the tumor microenvironment and is associated with poor patient outcomes. Here, we demonstrate that the deletion of the suppressor of cytokine signaling 3 (SOCS3) in T cells potentiates anti-tumor immune responses by conferring the anti-tumorigenic function of IL-6 in mouse and human models. In Socs3-deficient CD8
Language	English
Publishing date	2023-08-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112940
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: In Vitro

Yamamoto, Shinichi / Matsui, Ako / Ohyagi, Masaki / Kikutake, Chie / Harada, Yoshihiro / Iizuka-Koga, Mana / Suyama, Mikita / Yoshimura, Akihiko / Ito, Minako

Frontiers in immunology

2022 Volume 13, Page(s) 960036

Abstract: Regulatory T cells (Tregs) are normally born in the thymus and activated in secondary lymphoid tissues to suppress immune responses in the lymph node and at sites of inflammation. Tregs are also resident in various tissues or accumulate in damaged ... ...

Abstract	Regulatory T cells (Tregs) are normally born in the thymus and activated in secondary lymphoid tissues to suppress immune responses in the lymph node and at sites of inflammation. Tregs are also resident in various tissues or accumulate in damaged tissues, which are now called tissue Tregs, and contribute to homeostasis and tissue repair by interacting with non-immune cells. We have shown that Tregs accumulate in the brain during the chronic phase in a mouse cerebral infarction model, and these Tregs acquire the characteristic properties of brain Tregs and contribute to the recovery of neurological damage by interacting with astrocytes. However, the mechanism of tissue Treg development is not fully understood. We developed a culture method that confers brain Treg characteristics
MeSH term(s)	Animals ; Astrocytes/metabolism ; Brain ; Mice ; Receptors, Antigen, T-Cell ; Receptors, Serotonin/metabolism ; T-Lymphocytes, Regulatory
Chemical Substances	Receptors, Antigen, T-Cell ; Receptors, Serotonin
Language	English
Publishing date	2022-07-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.960036
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Article ; Online: Case Report: Countermeasures Against Heat and Coronavirus for Japanese Athletes at the Tokyo 2020 Olympics and Paralympic Games.

Nakamura, Mariko / Naito, Takashi / Saito, Tatsuya / Takahashi, Akari / Muraishi, Koji / Hakamada, Noriko / Otomo, Mana / Iizuka, Satoshi / Nakamura, Daisuke / Takahashi, Hideyuki

Frontiers in sports and active living

2022 Volume 4, Page(s) 878022

Abstract: The Tokyo 2020 Olympics and Paralympic Games were held in the hottest environment in the history of the games. Additionally, the worldwide coronavirus disease 2019 (COVID-19) pandemic necessitated daily polymerase chain reaction (PCR) testing during the ... ...

Abstract	The Tokyo 2020 Olympics and Paralympic Games were held in the hottest environment in the history of the games. Additionally, the worldwide coronavirus disease 2019 (COVID-19) pandemic necessitated daily polymerase chain reaction (PCR) testing during the games, wearing a mask became mandatory publicly, and it was an unheard and unique Olympic with no spectators. Heat acclimation, hydration, and body cooling are essential for safe and high-performance activities in hot environments. In 2015, the Japan Institute of Sports Sciences launched the "Heat Countermeasure Project" to conduct experiments and practical research on heat countermeasures and investigate issues related to heat countermeasures in each athletic event. The results obtained were proposed to various Japan national sports teams, and support for heat countermeasures for the Tokyo 2020 games was promoted in consultation with national federations. Furthermore, due to the COVID-19 pandemic, infectious disease countermeasures for the Tokyo 2020 Games during support were a must. Moreover, athletes, coaches, and team staff could not avoid implementing heat countermeasures while adopting measures against infectious diseases. This study aimed to clarify the issues faced with heat countermeasures and report on heat acclimation training and cooling support efforts, considering measures against infectious diseases.
Language	English
Publishing date	2022-06-06
Publishing country	Switzerland
Document type	Case Reports
ISSN	2624-9367
ISSN (online)	2624-9367
DOI	10.3389/fspor.2022.878022
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Article ; Online: Case Report

Mariko Nakamura / Takashi Naito / Tatsuya Saito / Akari Takahashi / Koji Muraishi / Noriko Hakamada / Mana Otomo / Satoshi Iizuka / Daisuke Nakamura / Hideyuki Takahashi

Frontiers in Sports and Active Living, Vol

Countermeasures Against Heat and Coronavirus for Japanese Athletes at the Tokyo 2020 Olympics and Paralympic Games

2022 Volume 4

Abstract	The Tokyo 2020 Olympics and Paralympic Games were held in the hottest environment in the history of the games. Additionally, the worldwide coronavirus disease 2019 (COVID-19) pandemic necessitated daily polymerase chain reaction (PCR) testing during the games, wearing a mask became mandatory publicly, and it was an unheard and unique Olympic with no spectators. Heat acclimation, hydration, and body cooling are essential for safe and high-performance activities in hot environments. In 2015, the Japan Institute of Sports Sciences launched the “Heat Countermeasure Project” to conduct experiments and practical research on heat countermeasures and investigate issues related to heat countermeasures in each athletic event. The results obtained were proposed to various Japan national sports teams, and support for heat countermeasures for the Tokyo 2020 games was promoted in consultation with national federations. Furthermore, due to the COVID-19 pandemic, infectious disease countermeasures for the Tokyo 2020 Games during support were a must. Moreover, athletes, coaches, and team staff could not avoid implementing heat countermeasures while adopting measures against infectious diseases. This study aimed to clarify the issues faced with heat countermeasures and report on heat acclimation training and cooling support efforts, considering measures against infectious diseases.
Keywords	cooling ; COVID-19 ; elite athletes ; heat acclimation ; Olympics ; Sports ; GV557-1198.995
Subject code	796
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Anti-human-TIGIT agonistic antibody ameliorates autoimmune diseases by inhibiting Tfh and Tph cells and enhancing Treg cells.

Kojima, Marenori / Suzuki, Katsuya / Takeshita, Masaru / Ohyagi, Masaki / Iizuka, Mana / Yamane, Humitsugu / Koga, Keiko / Kouro, Taku / Kassai, Yoshiaki / Yoshihara, Tomoki / Adachi, Ryutaro / Hashikami, Kentarou / Ota, Yuichiro / Yoshimoto, Keiko / Kaneko, Yuko / Morita, Rimpei / Yoshimura, Akihiko / Takeuchi, Tsutomu

Communications biology

2023 Volume 6, Issue 1, Page(s) 500

Abstract: T cells play important roles in autoimmune diseases, but it remains unclear how to optimally manipulate them. We focused on the T cell immunoreceptor with Ig and ITIM domains (TIGIT), a coinhibitory molecule that regulates and is expressed in T cells. In ...

Abstract	T cells play important roles in autoimmune diseases, but it remains unclear how to optimally manipulate them. We focused on the T cell immunoreceptor with Ig and ITIM domains (TIGIT), a coinhibitory molecule that regulates and is expressed in T cells. In autoimmune diseases, the association between TIGIT-expressing cells and pathogenesis and the function of human-TIGIT (hu-TIGIT) signalling modification have not been fully elucidated. Here we generated anti-hu-TIGIT agonistic monoclonal antibodies (mAbs) and generated hu-TIGIT knock-in mice to accurately evaluate the efficacy of mAb function. Our mAb suppressed the activation of CD4
MeSH term(s)	Animals ; Mice ; T-Lymphocytes, Regulatory ; Autoimmune Diseases/drug therapy ; Signal Transduction ; Antibodies, Monoclonal/pharmacology ; Receptors, Immunologic/genetics
Chemical Substances	Antibodies, Monoclonal ; Receptors, Immunologic
Language	English
Publishing date	2023-05-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-023-04874-3
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Article ; Online: Is Increased Kicking Leg Iliopsoas Muscle Tightness a Predictive Factor for Developing Spondylolysis in Adolescent Male Soccer Players?

Takei, Seira / Torii, Suguru / Taketomi, Shuji / Iwanuma, Soichiro / Tojima, Michio / Otomo, Mana / Iizuka, Satoshi / Tanaka, Sakae

Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine

2021 Volume 32, Issue 2, Page(s) e165–e171

Abstract: Objective: To identify predictive risk factors of lumbar stress (LS) fracture developing from an asymptomatic stress reaction of the pedicle among adolescent male soccer players.: Design: Prospective cohort study.: Setting: Amateur Japanese ... ...

Abstract	Objective: To identify predictive risk factors of lumbar stress (LS) fracture developing from an asymptomatic stress reaction of the pedicle among adolescent male soccer players. Design: Prospective cohort study. Setting: Amateur Japanese adolescent male soccer team. Participants: Japanese adolescent male soccer players (n = 195) aged 12 to 13 years. Assessment of risk factors independent variables: Height, body weight, body mass index, muscle tightness of both lower extremities (iliopsoas, hamstrings, and quadriceps), lumbar bone mineral content, developmental age, and lumbar lordosis angle were measured as baseline measurements. Main outcome measures dependent variable: Players who were diagnosed with an asymptomatic stress reaction of the lumbar spine pedicle at baseline were followed; extension-based lumbar pain was defined 1 year after the baseline. The players were assigned to the LS fracture or control (CON) group at follow-up. Results: At baseline, 40 boys were diagnosed with an asymptomatic stress reaction of the lumbar spine pedicle. The difference in muscle tightness between the kicking leg and supporting leg was significantly different (P = 0.012) between the LS (n = 16) and CON (n = 22) groups. Increase in iliopsoas muscle tightness in the kicking leg was a predictive risk factor of developing extension-based lumbar pain after adjusting for developmental age and body mass index (odds ratio, 1.54; 95% confidence interval, 1.05-2.27). Conclusions: Development of extension-based lumbar pain from an asymptomatic stress reaction of the pedicle among adolescent male soccer players was associated with increased iliopsoas muscle tightness of the kicking leg relative to that of the supporting leg.
MeSH term(s)	Adolescent ; Cohort Studies ; Fractures, Stress/epidemiology ; Fractures, Stress/etiology ; Humans ; Japan/epidemiology ; Leg/physiology ; Low Back Pain/etiology ; Lumbar Vertebrae/injuries ; Male ; Muscle Tonus ; Prospective Studies ; Risk Factors ; Soccer/physiology ; Spinal Fractures/epidemiology ; Spinal Fractures/etiology
Language	English
Publishing date	2021-03-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1062530-6
ISSN	1536-3724 ; 1050-642X
ISSN (online)	1536-3724
ISSN	1050-642X
DOI	10.1097/JSM.0000000000000920
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Zs.A 3120: Show issues

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Article ; Online: Development and Functional Modulation of Regulatory T Cells by Transcription Factors and Epigenetics.

Ito, Minako / Iizuka-Koga, Mana / Ando, Makoto / Yoshimura, Akihiko

Cornea

2018 Volume 37 Suppl 1, Page(s) S42–S49

Abstract: Regulatory T cells (Tregs) are essential for the maintenance of immune homeostasis. Studies of Treg are not only necessary for understanding the mechanism of immune homeostasis but also extremely useful for the development of treatments of various immune ...

Abstract	Regulatory T cells (Tregs) are essential for the maintenance of immune homeostasis. Studies of Treg are not only necessary for understanding the mechanism of immune homeostasis but also extremely useful for the development of treatments of various immune diseases. Forkhead box P3 (Foxp3) was identified as the master gene responsible for the immune-suppressing activity of Tregs. The promoter region and several intronic enhancers, designated conserved noncoding sequence (CNS) 0, 1, 2, and 3, at the Foxp3 gene locus have important roles in Foxp3 expression and Treg development. We demonstrated that transcription factors Nr4a and Smad2/3 are required for development of thymic Tregs and induced Tregs, respectively. In addition to transcription factors, Treg-specific DNA demethylation has been shown to be important for Treg stability. In particular, DNA demethylation of CNS2 was implicated in Treg stability, and members of the ten-eleven translocation family of demethylation factors were recently demonstrated to have important roles in 5'-C-phosphate-G-3' demethylation at CNS2. This article summarizes recent findings regarding the roles of transcription factors and epigenetic modifications in the differentiation, maintenance, and function of Tregs. This review will facilitate clinical application of Tregs to diseases in the field of ophthalmology, including uveitis and age-related macular degeneration.
MeSH term(s)	Epigenomics ; Eye Diseases/genetics ; Eye Diseases/immunology ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/physiology ; Gene Expression Regulation/physiology ; Humans ; Nuclear Receptor Subfamily 4, Group A, Member 1/physiology ; Ophthalmology ; Promoter Regions, Genetic/physiology ; RNA, Untranslated ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	Forkhead Transcription Factors ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; RNA, Untranslated
Language	English
Publishing date	2018-09-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604826-2
ISSN	1536-4798 ; 0277-3740
ISSN (online)	1536-4798
ISSN	0277-3740
DOI	10.1097/ICO.0000000000001720
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Zs.A 1790: Show issues

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Article ; Online: Regulatory T Cells: Pathophysiological Roles and Clinical Applications.

Sakai, Ryota / Komai, Kyoko / Iizuka-Koga, Mana / Yoshimura, Akihiko / Ito, Minako

The Keio journal of medicine

2019 Volume 69, Issue 1, Page(s) 1–15

Abstract: Inflammation and immune responses after tissue injury play pivotal roles in the resolution of inflammation, tissue recovery, fibrosis, and remodeling. Regulatory T cells (Tregs) are responsible for immune tolerance and are usually activated in secondary ... ...

Abstract	Inflammation and immune responses after tissue injury play pivotal roles in the resolution of inflammation, tissue recovery, fibrosis, and remodeling. Regulatory T cells (Tregs) are responsible for immune tolerance and are usually activated in secondary lymphatic tissues. Activated Tregs subsequently regulate effector T cell and dendritic cell activation. For clinical applications such as the suppression of both autoimmune diseases and the rejection of transplanted organs, methods to generate stabilized antigen-specific Tregs are required. For this purpose, transcriptional and epigenetic regulation of Foxp3 expression has been investigated. In addition to conventional Tregs, there are some Tregs that reside in tissues and are called tissue Tregs. Tissue Tregs exhibit tissue-specific functions that contribute to the maintenance of tissue homeostasis and repair. Such tissue Tregs could also be useful for Treg-based cell therapy. We recently discovered brain Tregs that accumulate in the brain during the chronic phase of ischemic brain injury. Brain Tregs resemble other tissue Tregs, but are unique in expressing neural cell-specific genes such as the serotonin receptor (Htr7); consequently, brain Tregs respond to serotonin. Here, we describe our experiences in the use of Tregs to suppress graft-versus-host disease and to promote neural recovery after stroke.
MeSH term(s)	Animals ; Brain/immunology ; Brain Ischemia/immunology ; Central Nervous System Diseases/immunology ; DNA Methylation ; Forkhead Transcription Factors/genetics ; Graft vs Host Disease/prevention & control ; Humans ; Mice ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/physiology
Chemical Substances	FOXP3 protein, human ; Forkhead Transcription Factors
Language	English
Publishing date	2019-07-26
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	390981-5
ISSN	1880-1293 ; 0022-9717
ISSN (online)	1880-1293
ISSN	0022-9717
DOI	10.2302/kjm.2019-0003-OA
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Article ; Online: Single-Cell Analysis Revealed the Role of CD8

Komai, Kyoko / Ito, Minako / Nomura, Seitaro / Shichino, Shigeyuki / Katoh, Manami / Yamada, Shintaro / Ko, Toshiyuki / Iizuka-Koga, Mana / Nakatsukasa, Hiroko / Yoshimura, Akihiko

Frontiers in immunology

2021 Volume 12, Page(s) 763647

Abstract: Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. Heart-resident and infiltrated macrophages have been shown to play important roles in the cardiac remodeling that occurs in response to cardiac pressure overload. ...

Abstract	Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. Heart-resident and infiltrated macrophages have been shown to play important roles in the cardiac remodeling that occurs in response to cardiac pressure overload. However, the possible roles of T cells in this process, have not been well characterized. Here we show that T cell depletion conferred late-stage heart protection but induced cardioprotective hypertrophy at an early stage of heart failure caused by cardiac pressure overload. Single-cell RNA sequencing analysis revealed that CD8
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/physiology ; Cardiomegaly/etiology ; Cell Differentiation ; Disease Models, Animal ; Heart Failure/immunology ; Macrophages/cytology ; Macrophages/physiology ; Mice ; Mice, Inbred C57BL ; Single-Cell Analysis/methods
Language	English
Publishing date	2021-10-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.763647
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Article ; Online: Induction and maintenance of regulatory T cells by transcription factors and epigenetic modifications.

Iizuka-Koga, Mana / Nakatsukasa, Hiroko / Ito, Minako / Akanuma, Takashi / Lu, Qianjin / Yoshimura, Akihiko

Journal of autoimmunity

2017 Volume 83, Page(s) 113–121

Abstract: Regulatory T cells (Tregs) are an essential cell subset for the maintenance of immune homeostasis. Foxp3 (Forkhead box P3) is the Treg master gene which is essential for immune suppressing activity. In addition, Tregs are characterized by a distinct ... ...

Abstract	Regulatory T cells (Tregs) are an essential cell subset for the maintenance of immune homeostasis. Foxp3 (Forkhead box P3) is the Treg master gene which is essential for immune suppressing activity. In addition, Tregs are characterized by a distinct pattern of gene expression, including upregulation of immune-suppressive genes and silencing of inflammatory genes. The molecular mechanisms of Treg development and maintenance have been intensively investigated. Tregs are characterized by expression of the transcription factor Foxp3. Several intronic enhancers and a promoter at the Foxp3 gene locus were shown to play important roles in Treg differentiation. The enhancers have been designated as conserved non-coding sequences (CNSs) 0, 1, 2, and 3. We showed that the transcription factors Nr4a and Smad2/3 are essential for the development of thymic Tregs and induced Tregs, respectively. Recently, Treg-specific DNA demethylation has been shown to play an important role in Treg stability. DNA demethylation of CNS2 has been implicated in Treg stability, and recent reports have revealed that the ten-eleven translocation (Tet) family of demethylation factor plays an important role in CpG demethylation at CNS2. This article reviews the recent progress on the roles of transcription factors and epigenetic modifications in the differentiation, maintenance, and function of Tregs.
Language	English
Publishing date	2017-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	639452-8
ISSN	1095-9157 ; 0896-8411
ISSN (online)	1095-9157
ISSN	0896-8411
DOI	10.1016/j.jaut.2017.07.002
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