The Experts below are selected from a list of 192 Experts worldwide ranked by ideXlab platform
Guoliang Cui - One of the best experts on this subject based on the ideXlab platform.
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Regulatory T cells sense effector T‐cell activation through synchronized JunB expression
FEBS letters, 2019Co-Authors: Agnes Hotz-wagenblatt, Peter Angel, Kerstin Mohr, Tilo Schlimbach, Michael Schmitt, Guoliang CuiAbstract:To maintain immune tolerance, effector T-cell (Teff) responses must be checked by the regulatory T cells (Tregs) in time. It remains incompletely understood how Tregs sense real-time Teff activation. Here, we report that the AP-1 Transcription Factor JunB, which is induced in Teffs upon T-cell receptor (TCR) activation, is also increased in Tregs by TCR stimuli. Treg-specific deletion of JunB impairs Treg identity, causes uncontrolled inflammatory cytokine production by Teffs and leads to the T-box Transcription Factor T-bet-dependent spontaneous inflammation. Furthermore, JunB deficiency in Tregs unleashes antitumor Teff responses in a mouse model of melanoma. We conclude that JunB alarms Tregs of the emerging Teff activation and synchronizes immune regulation with the immune reaction in autoimmunity and cancer.
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regulatory t cells sense effector t cell activation through synchronized JunB expression
FEBS Letters, 2019Co-Authors: Agnes Hotzwagenblatt, Peter Angel, Kerstin Mohr, Tilo Schlimbach, Michael Schmitt, Guoliang CuiAbstract:To maintain immune tolerance, effector T-cell (Teff) responses must be checked by the regulatory T cells (Tregs) in time. It remains incompletely understood how Tregs sense real-time Teff activation. Here, we report that the AP-1 Transcription Factor JunB, which is induced in Teffs upon T-cell receptor (TCR) activation, is also increased in Tregs by TCR stimuli. Treg-specific deletion of JunB impairs Treg identity, causes uncontrolled inflammatory cytokine production by Teffs and leads to the T-box Transcription Factor T-bet-dependent spontaneous inflammation. Furthermore, JunB deficiency in Tregs unleashes antitumor Teff responses in a mouse model of melanoma. We conclude that JunB alarms Tregs of the emerging Teff activation and synchronizes immune regulation with the immune reaction in autoimmunity and cancer.
Jianxin Sun - One of the best experts on this subject based on the ideXlab platform.
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MicroRNA-663 regulates human vascular smooth muscle cell phenotypic switch and vascular neointimal formation.
Circulation research, 2013Co-Authors: Ni Zhu, Nadan Wang, Ming Chen, Xiaohua You, Xianxian Zhao, Charalambos C. Solomides, Yong-wen Qin, Jianxin SunAbstract:Rationale: Abnormal phenotypic switch of vascular smooth muscle cell (VSMC) is a hallmark of vascular disorders such as atherosclerosis and restenosis after angioplasty. MicroRNAs (miRNAs) have emerged as important regulators for VSMC function, and we recently identified miR-663 as critical for controlling human aortic smooth muscle cell proliferation. Objective: To investigate whether miR-663 plays a role in human VSMC phenotypic switch and the development of neointima formation. Methods and Results: By using quantitative reverse-Transcription polymerase chain reaction, we found that miR-663 was significantly downregulated in human aortic VSMCs on platelet-derived growth Factor treatment, whereas expression was markedly increased during VSMC differentiation. Furthermore, we demonstrated that overexpression of miR-663 increased expression of VSMC differentiation marker genes, such as smooth muscle 22α, smooth muscle α-actin, calponin, and smooth muscle myosin heavy chain, and potently inhibited platelet-derived growth Factor–induced VSMC proliferation and migration. We identified the Transcription Factor JunB and myosin light chain 9 as downstream targets of miR-663 in human VSMCs, because overexpression of miR-663 markedly inhibited expression of JunB and its downstream molecules, such as myosin light chain 9 and matrix metalloproteinase 9. Finally, we showed that adeno-miR-663 markedly suppressed the neointimal lesion formation by ≈50% in mice after vascular injury induced by carotid artery ligation, specifically via decreased JunB expression. Conclusions: These results indicate that miR-663 is a novel modulator of human VSMC phenotypic switch by targeting JunB/myosin light chain 9 expression. These findings suggest that targeting miR-663 or its specific downstream targets in human VSMCs may represent an attractive approach for the treatment of proliferative vascular diseases.
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Abstract 212: MicroRNA-663 is a Novel Regulator of Human Vascular Smooth Muscle Cell Phenotypic Switch in vitro and Neointimal Formation in vivo
Arteriosclerosis Thrombosis and Vascular Biology, 2013Co-Authors: Qing Qin, Ming Chen, Xiaohua You, Xianxian Zhao, Yong-wen Qin, Jianxin SunAbstract:Background Abnormal phenotypic switch of vascular smooth muscle cell (VSMC) is a hallmark of vascular disorders such as atherosclerosis and restenosis after angioplasty. Recently, microRNAs (miRNAs) emerge as critical regulators for vascular smooth muscle cell (VSMC) function. Our initial study identified miR-663 as one of the most sharply downregulated miRNAs in human proliferative aortic smooth muscle cells. Hypothesis MiR-663 is implicated in human VSMC phenotypic switch and the development of neointima formation. Methods and Results By using quantitative real-time PCR (qRT-PCR), we found that microRNA-663 (miR-663) was significantly downregulated in cultured human aortic VSMCs upon platelet-derived growth Factor (PDGF) treatment, whereas its expression was markedly increased during VSMC differentiation as induced by either retinoid acid or SMC differentiation medium, a condition which induces SMC differentiation and inhibits cell proliferation. Furthermore, we demonstrated that overexpression of miR-663 significantly increased the expression of VSMC differentiation marker genes, such as SM22α, SM α-action, calponin, and SM myosin heavy chain, suggesting that miR-663 is a novel modulator implicated in human VSMC phenotypic switch. Moreover, miR-663 potently inhibited PDGF induced VSMC proliferation and migration. Mechanistically, we identified JunB as a downstream target of miR-663 in human VSMCs. Indeed, overexpression of miR-663 markedly inhibited the expression of the Transcription Factor JunB as well as its downstream molecules including matrix metallopeptidase-9 (MMP-9) and myosin light chain-9 (Myl9), thus inhibiting VSMC proliferation and migration. Finally, we showed that adeno-miR-663 markedly suppressed the neointimal lesion formation by approximately 50% in mice after vascular injury induced by carotid artery ligation, specifically via decreased JunB expression. Conclusion These results indicate that miR-663 is a novel modulator implicated in human VSMC phenotypic switch through targeting JunB expression and suggest that specific modulation of miR-663 in human VSMCs may represent a novel and attractive approach for the treatment of vascular proliferative diseases.
Kristina M Miller - One of the best experts on this subject based on the ideXlab platform.
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species and sex specific responses and recovery of wild mature pacific salmon to an exhaustive exercise and air exposure stressor
Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 2014Co-Authors: Michael R Donaldson, Scott G Hinch, Ken M Jeffries, David A Patterson, Steven J Cooke, Anthony P Farrell, Kristina M MillerAbstract:article i nfo Despite the common mechanisms that underlie vertebrate responses to exhaustive exercise stress, the magnitude and the timecourse of recovery can be context-specific. Here, we examine how wild, adult male and female pink (Oncorhynchus gorbuscha )a nd sockeye (Oncorhynchus nerka) salmon respond to and recover from an exhaustive exercise and air exposure stressor, designed to simulate fisheries capture and handling. We follow gill tissue gene expression for genes active in cellular stress, cell maintenance, and apoptosis as well as plasma osmoregulatory, stress, and reproductive indices. The stressor initiateda major stress response as indicatedby increasednormalised expression of two stress-responsive genes, Transcription Factor JunB and cytochrome C (pink salmon only). The stressor resulted in increased plasma ion cortisol, lactate, and depressed estradiol (sockeye salmon only). Gene ex- pression and plasma variables showed a general recovery by 24 h post-stressor. Species- and sex-specifi cp atterns were observed in stress responseand recovery, withpinksalmonmountinga higher magnitude stress response for plasma variables and sockeye salmon exhibiting a higher and more variable gene expression profile. These results highlight species- and sex-specific responses of migrating Pacific salmon to simulated fisheries encounters, which contribute new knowledge towards understanding the consequences of fisheries capture-and-release.
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Species- and sex-specific responses and recovery of wild, mature pacific salmon to an exhaustive exercise and air exposure stressor.
Comparative biochemistry and physiology. Part A Molecular & integrative physiology, 2014Co-Authors: Michael R Donaldson, Scott G Hinch, Ken M Jeffries, David A Patterson, Steven J Cooke, Anthony P Farrell, Kristina M MillerAbstract:Despite the common mechanisms that underlie vertebrate responses to exhaustive exercise stress, the magnitude and the timecourse of recovery can be context-specific. Here, we examine how wild, adult male and female pink (Oncorhynchus gorbuscha) and sockeye (Oncorhynchus nerka) salmon respond to and recover from an exhaustive exercise and air exposure stressor, designed to simulate fisheries capture and handling. We follow gill tissue gene expression for genes active in cellular stress, cell maintenance, and apoptosis as well as plasma osmoregulatory, stress, and reproductive indices. The stressor initiated a major stress response as indicated by increased normalised expression of two stress-responsive genes, Transcription Factor JunB and cytochrome C (pink salmon only). The stressor resulted in increased plasma ion cortisol, lactate, and depressed estradiol (sockeye salmon only). Gene expression and plasma variables showed a general recovery by 24h post-stressor. Species- and sex-specific patterns were observed in stress response and recovery, with pink salmon mounting a higher magnitude stress response for plasma variables and sockeye salmon exhibiting a higher and more variable gene expression profile. These results highlight species- and sex-specific responses of migrating Pacific salmon to simulated fisheries encounters, which contribute new knowledge towards understanding the consequences of fisheries capture-and-release.
Michael R Donaldson - One of the best experts on this subject based on the ideXlab platform.
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species and sex specific responses and recovery of wild mature pacific salmon to an exhaustive exercise and air exposure stressor
Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 2014Co-Authors: Michael R Donaldson, Scott G Hinch, Ken M Jeffries, David A Patterson, Steven J Cooke, Anthony P Farrell, Kristina M MillerAbstract:article i nfo Despite the common mechanisms that underlie vertebrate responses to exhaustive exercise stress, the magnitude and the timecourse of recovery can be context-specific. Here, we examine how wild, adult male and female pink (Oncorhynchus gorbuscha )a nd sockeye (Oncorhynchus nerka) salmon respond to and recover from an exhaustive exercise and air exposure stressor, designed to simulate fisheries capture and handling. We follow gill tissue gene expression for genes active in cellular stress, cell maintenance, and apoptosis as well as plasma osmoregulatory, stress, and reproductive indices. The stressor initiateda major stress response as indicatedby increasednormalised expression of two stress-responsive genes, Transcription Factor JunB and cytochrome C (pink salmon only). The stressor resulted in increased plasma ion cortisol, lactate, and depressed estradiol (sockeye salmon only). Gene ex- pression and plasma variables showed a general recovery by 24 h post-stressor. Species- and sex-specifi cp atterns were observed in stress responseand recovery, withpinksalmonmountinga higher magnitude stress response for plasma variables and sockeye salmon exhibiting a higher and more variable gene expression profile. These results highlight species- and sex-specific responses of migrating Pacific salmon to simulated fisheries encounters, which contribute new knowledge towards understanding the consequences of fisheries capture-and-release.
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Species- and sex-specific responses and recovery of wild, mature pacific salmon to an exhaustive exercise and air exposure stressor.
Comparative biochemistry and physiology. Part A Molecular & integrative physiology, 2014Co-Authors: Michael R Donaldson, Scott G Hinch, Ken M Jeffries, David A Patterson, Steven J Cooke, Anthony P Farrell, Kristina M MillerAbstract:Despite the common mechanisms that underlie vertebrate responses to exhaustive exercise stress, the magnitude and the timecourse of recovery can be context-specific. Here, we examine how wild, adult male and female pink (Oncorhynchus gorbuscha) and sockeye (Oncorhynchus nerka) salmon respond to and recover from an exhaustive exercise and air exposure stressor, designed to simulate fisheries capture and handling. We follow gill tissue gene expression for genes active in cellular stress, cell maintenance, and apoptosis as well as plasma osmoregulatory, stress, and reproductive indices. The stressor initiated a major stress response as indicated by increased normalised expression of two stress-responsive genes, Transcription Factor JunB and cytochrome C (pink salmon only). The stressor resulted in increased plasma ion cortisol, lactate, and depressed estradiol (sockeye salmon only). Gene expression and plasma variables showed a general recovery by 24h post-stressor. Species- and sex-specific patterns were observed in stress response and recovery, with pink salmon mounting a higher magnitude stress response for plasma variables and sockeye salmon exhibiting a higher and more variable gene expression profile. These results highlight species- and sex-specific responses of migrating Pacific salmon to simulated fisheries encounters, which contribute new knowledge towards understanding the consequences of fisheries capture-and-release.
Soh Yamazaki - One of the best experts on this subject based on the ideXlab platform.
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Regulation of T cell differentiation by the AP-1 Transcription Factor JunB.
Immunological medicine, 2021Co-Authors: Takaharu Katagiri, Hideto Kameda, Hiroyasu Nakano, Soh YamazakiAbstract:JunB, a component of the activator protein-1 (AP-1) Transcription Factor, is known to exhibit an important role in bone formation and bone marrow cell proliferation. During T helper type 2 (Th2) ce...
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regulation of t cell differentiation by the ap 1 Transcription Factor JunB
Immunological medicine, 2021Co-Authors: Takaharu Katagiri, Hideto Kameda, Hiroyasu Nakano, Soh YamazakiAbstract:JunB, a component of the activator protein-1 (AP-1) Transcription Factor, is known to exhibit an important role in bone formation and bone marrow cell proliferation. During T helper type 2 (Th2) cell differentiation, JunB contributes to the regulation of interleukin (IL)-4 expression, and AP-1 and nuclear Factor of activated T cell (NFAT) constitute a heteromer and contribute to IL-2 production. However, the role of JunB in other T cells has not been investigated. In 2017, it was revealed that JunB, in collaboration with basic leucine zipper ATF-like Transcription Factor (BATF), regulates the expression of Th17-related genes. Furthermore, JunB was found to play an important role in regulatory T (Treg) cell differentiation, contributing to CD25 expression and IL-2 production. IL-2 is a T cell activator and has been shown as a necessary Factor for Treg proliferation. Here, we review the role of JunB in T cells based on basic research data and discuss the potential for its clinical applications.
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JunB plays a crucial role in development of regulatory T cells by promoting IL-2 signaling
Mucosal Immunology, 2019Co-Authors: Takaharu Katagiri, Soh Yamazaki, Yuto Fukui, Kotaro Aoki, Hideo Yagita, Takashi Nishina, Tetuo Mikami, Sayaka Katagiri, Ayako Shiraishi, Soichiro KimuraAbstract:The AP-1 Transcription Factor JunB plays crucial roles in multiple biological processes, including placental formation and bone homeostasis. We recently reported that JunB is essential for development of Th17 cells, and thus JunB -deficient mice are resistant to experimental autoimmune encephalomyelitis. However, the role of JunB in CD4^+ T cells under other inflammatory disease conditions is unknown. Here we show that mice lacking JunB in CD4^+ T cells ( JunB ^fl/fl Cd4-Cre mice) were more susceptible to dextran sulfate sodium (DSS)-induced colitis because of impaired development of regulatory T (Treg) cells. Production of interleukin (IL)-2 and expression of CD25, a high affinity IL-2 receptor component, were decreased in JunB -deficient CD4^+ T cells in vitro and in vivo. Naive CD4^+ T cells from JunB ^fl/fl Cd4-Cre mice failed to differentiate into Treg cells in the absence of exogenously added IL-2 in vitro. A mixed bone marrow transfer experiment revealed that defective Treg development of JunB -deficient CD4^+ T cells was not rescued by co-transferred wild-type cells, indicating a significance of the cell-intrinsic defect. Injection of IL-2-anti-IL-2 antibody complexes induced expansion of Treg cells and alleviated DSS-induced colitis in JunB ^fl/fl Cd4-Cre mice. Thus JunB plays a crucial role in the development of Treg cells by facilitating IL-2 signaling.
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The AP-1 Transcription Factor JunB is required for Th17 cell differentiation
Scientific reports, 2017Co-Authors: Soh Yamazaki, Takaharu Katagiri, Yoshihiko Tanaka, Hiromitsu Araki, Akira Kohda, Fumiyuki Sanematsu, Tomoko Arasaki, Xuefeng Duan, Fumihito Miura, Ryodai ShindoAbstract:Interleukin (IL)-17-producing T helper (Th17) cells are crucial for host defense against extracellular microbes and pathogenesis of autoimmune diseases. Here we show that the AP-1 Transcription Factor JunB is required for Th17 cell development. JunB-deficient CD4+ T cells are able to develop in vitro into various helper T subsets except Th17. The RNA-seq transcriptome analysis reveals that JunB is crucial for the Th17-specific gene expression program. JunB-deficient mice are completely resistant to experimental autoimmune encephalomyelitis, a Th17-mediated inflammatory disease, and naive T helper cells from such mice fail to differentiate into Th17 cells. JunB appears to activate Th17 signature genes by forming a heterodimer with BATF, another AP-1 Factor essential for Th17 differentiation. The mechanism whereby JunB controls Th17 cell development likely involves activation of the genes for the Th17 lineage-specifying orphan receptors RORγt and RORα and reduced expression of Foxp3, a Transcription Factor known to antagonize RORγt function.