The Tokushima journal of experimental medicine最新文献

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Tumors with TSC mutations are sensitive to CDK7 inhibition through NRF2 and glutathione depletion. TSC突变的肿瘤通过NRF2和谷胱甘肽耗竭对CDK7抑制敏感。
The Tokushima journal of experimental medicine Pub Date : 2019-11-04 Epub Date: 2019-09-10 DOI: 10.1084/jem.20190251
Mahsa Zarei, Heng Du, Amin H Nassar, Rachel E Yan, Krinio Giannikou, Sneha H Johnson, Hilaire C Lam, Elizabeth P Henske, Yubao Wang, Tinghu Zhang, John Asara, David J Kwiatkowski
{"title":"Tumors with TSC mutations are sensitive to CDK7 inhibition through NRF2 and glutathione depletion.","authors":"Mahsa Zarei, Heng Du, Amin H Nassar, Rachel E Yan, Krinio Giannikou, Sneha H Johnson, Hilaire C Lam, Elizabeth P Henske, Yubao Wang, Tinghu Zhang, John Asara, David J Kwiatkowski","doi":"10.1084/jem.20190251","DOIUrl":"10.1084/jem.20190251","url":null,"abstract":"<p><p>Tuberous sclerosis complex (TSC) is characterized by tumor development in the brain, heart, kidney, and lungs. In TSC tumors, loss of the TSC1/TSC2 protein complex leads to activation of mTORC1 with downstream effects on anabolism and cell growth. Because mTORC1 activation enhances mRNA transcription, we hypothesized that aberrant mTORC1 activation might confer TSC-null cell dependence on transcriptional regulation. We demonstrate that TSC1- or TSC2-null cells, in contrast to their wild-type counterparts, are sensitive to pharmacological inhibition of CDK7. Mechanistic studies revealed that CDK7 inhibition markedly reduces glutathione levels and increases reactive oxygen species due to reduced expression of NRF2 and glutathione biosynthesis genes. Treatment of both <i>Tsc2<sup>+/</sup></i> <sup>-</sup> mice and a TSC1-null bladder cancer xenograft model with a CDK7 inhibitor showed marked reduction in tumor volume and absence of regrowth in the xenograft model. These results suggest that CDK7 inhibition is a promising therapeutic approach for treatment of TSC-associated tumors and cancers with mutations in either <i>TSC1</i> or <i>TSC2</i>.</p>","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"216 1","pages":"2635-2652"},"PeriodicalIF":0.0,"publicationDate":"2019-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75371534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Developmental and cellular age direct conversion of CD4+ T cells into RORγ+ or Helios+ colon Treg cells 发育和细胞年龄直接将CD4+ T细胞转化为RORγ+或Helios+结肠Treg细胞
The Tokushima journal of experimental medicine Pub Date : 2019-11-04 DOI: 10.1084/jem.20190428
Alvin Pratama, Alexandra Schnell, D. Mathis, C. Benoist
{"title":"Developmental and cellular age direct conversion of CD4+ T cells into RORγ+ or Helios+ colon Treg cells","authors":"Alvin Pratama, Alexandra Schnell, D. Mathis, C. Benoist","doi":"10.1084/jem.20190428","DOIUrl":"https://doi.org/10.1084/jem.20190428","url":null,"abstract":"Using a polyclonal Treg cell replacement system, Pratama et al. show that naive Tconv cells have the capacity to convert into both RORγ+ and Helios+ Treg cells in the colon. The developmental maturity (or cell states) of the starting Tconv cells determines the phenotype of the resulting pTreg cells.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79360490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 47
TIPE2 specifies the functional polarization of myeloid-derived suppressor cells during tumorigenesis TIPE2指定肿瘤发生过程中髓源性抑制细胞的功能极化
The Tokushima journal of experimental medicine Pub Date : 2019-10-29 DOI: 10.1084/jem.20182005
Dehong Yan, Jing-Horng Wang, Honghong Sun, Aliyeh Zamani, Hongling Zhang, Weihong Chen, A. Tang, Qingguo Ruan, Xiaolu Yang, Youhai H. Chen, X. Wan
{"title":"TIPE2 specifies the functional polarization of myeloid-derived suppressor cells during tumorigenesis","authors":"Dehong Yan, Jing-Horng Wang, Honghong Sun, Aliyeh Zamani, Hongling Zhang, Weihong Chen, A. Tang, Qingguo Ruan, Xiaolu Yang, Youhai H. Chen, X. Wan","doi":"10.1084/jem.20182005","DOIUrl":"https://doi.org/10.1084/jem.20182005","url":null,"abstract":"In this study, Yan et al. demonstrate that TIPE2, which is induced by tumor-derived ROS, promotes the functional polarization of protumoral myeloid-derived suppressor cells (MDSCs) during tumorigenesis by specifying the expression of MDSC signature genes such as Cebpb.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77515241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 37
A DNAH17 missense variant causes flagella destabilization and asthenozoospermia DNAH17错义变异导致鞭毛不稳定和弱精子症
The Tokushima journal of experimental medicine Pub Date : 2019-10-28 DOI: 10.1084/jem.20182365
Beibei Zhang, Hui Ma, Teka Khan, Ao Ma, Tao Li, Huan Zhang, Jianing Gao, Jianteng Zhou, Yang Li, Changping Yu, Jianqiang Bao, Asim Ali, G. Murtaza, Hao Yin, Qian Gao, Xiaohua Jiang, Feng Zhang, Chunyu Liu, Ihsan Khan, Muhammad Zubair, H. M. Hussain, R. Khan, A. Yousaf, Limin Yuan, Yan Lu, Xiaoling Xu, Yun Wang, Qizhao Tao, QiaoMei Hao, Hui Fang, Hongtao Cheng, Yuanwei Zhang, Qinghua Shi
{"title":"A DNAH17 missense variant causes flagella destabilization and asthenozoospermia","authors":"Beibei Zhang, Hui Ma, Teka Khan, Ao Ma, Tao Li, Huan Zhang, Jianing Gao, Jianteng Zhou, Yang Li, Changping Yu, Jianqiang Bao, Asim Ali, G. Murtaza, Hao Yin, Qian Gao, Xiaohua Jiang, Feng Zhang, Chunyu Liu, Ihsan Khan, Muhammad Zubair, H. M. Hussain, R. Khan, A. Yousaf, Limin Yuan, Yan Lu, Xiaoling Xu, Yun Wang, Qizhao Tao, QiaoMei Hao, Hui Fang, Hongtao Cheng, Yuanwei Zhang, Qinghua Shi","doi":"10.1084/jem.20182365","DOIUrl":"https://doi.org/10.1084/jem.20182365","url":null,"abstract":"Using mice modelling patients’ variant, this study demonstrates that a homozygous DNAH17 missense variant causes asthenozoospermia and specifically destabilizes microtubule doublets 4–7 in flagella, which could be largely due to the storage of sperm in epididymis.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"279 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80109251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 82
Platelet-activating factor (PAF) mediates NLRP3-NEK7 inflammasome induction independently of PAFR 血小板活化因子(PAF)独立于PAFR介导NLRP3-NEK7炎性体诱导
The Tokushima journal of experimental medicine Pub Date : 2019-10-26 DOI: 10.1084/jem.20190111
Meng Deng, Haitao Guo, Jason W. Tam, Brandon M. Johnson, W. Brickey, James S. New, Austin R. Lenox, Hexin Shi, D. Golenbock, Beverly H. Koller, Karen P McKinnon, B. Beutler, Jenny P.-Y. Ting
{"title":"Platelet-activating factor (PAF) mediates NLRP3-NEK7 inflammasome induction independently of PAFR","authors":"Meng Deng, Haitao Guo, Jason W. Tam, Brandon M. Johnson, W. Brickey, James S. New, Austin R. Lenox, Hexin Shi, D. Golenbock, Beverly H. Koller, Karen P McKinnon, B. Beutler, Jenny P.-Y. Ting","doi":"10.1084/jem.20190111","DOIUrl":"https://doi.org/10.1084/jem.20190111","url":null,"abstract":"Platelet-activating factor (PAF) can drive pathophysiological inflammation, but the mechanism remains incompletely understood. Here, Deng et al. report that PAF activates the canonical NLRP3 inflammasome independently of its receptor PAFR.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"5 1","pages":"2838 - 2853"},"PeriodicalIF":0.0,"publicationDate":"2019-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72635852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 34
AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation 在T细胞活化过程中,共刺激诱导的AP-1活性是染色质打开所必需的
The Tokushima journal of experimental medicine Pub Date : 2019-10-25 DOI: 10.1084/jem.20182009
M. Yukawa, S. Jagannathan, Sushmitha Vallabh, A. Kartashov, Xiaoting Chen, M. Weirauch, A. Barski
{"title":"AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation","authors":"M. Yukawa, S. Jagannathan, Sushmitha Vallabh, A. Kartashov, Xiaoting Chen, M. Weirauch, A. Barski","doi":"10.1084/jem.20182009","DOIUrl":"https://doi.org/10.1084/jem.20182009","url":null,"abstract":"AP-1 transcription factor is recruited to the majority of chromatin remodeling sites during T cell activation. The activity of AP-1 is induced by co-stimulation and is required for chromatin opening. The sites of remodeling overlap with risk loci of immunological diseases.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90262831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 60
Cell type–specific actions of Bcl11b in early T-lineage and group 2 innate lymphoid cells Bcl11b在早期t系和2组先天淋巴样细胞中的细胞类型特异性作用
The Tokushima journal of experimental medicine Pub Date : 2019-10-25 DOI: 10.1084/jem.20190972
H. Hosokawa, Maile Romero-Wolf, Qi Yang, Y. Motomura, D. Levanon, Y. Groner, K. Moro, Tomoaki Tanaka, E. Rothenberg
{"title":"Cell type–specific actions of Bcl11b in early T-lineage and group 2 innate lymphoid cells","authors":"H. Hosokawa, Maile Romero-Wolf, Qi Yang, Y. Motomura, D. Levanon, Y. Groner, K. Moro, Tomoaki Tanaka, E. Rothenberg","doi":"10.1084/jem.20190972","DOIUrl":"https://doi.org/10.1084/jem.20190972","url":null,"abstract":"Bcl11b binds to distinctive genomic regions with different partners and regulates completely different target genes in pro-T and ILC2 cells. Despite these divergences in Bcl11b function, a shared enhancer supports initial Bcl11b locus opening in both pro-T and ILC2 lineages.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82354579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 40
Nutrient mTORC1 signaling underpins regulatory T cell control of immune tolerance 营养mTORC1信号支持调节性T细胞控制免疫耐受
The Tokushima journal of experimental medicine Pub Date : 2019-10-24 DOI: 10.1084/jem.20190848
Mytrang H Do, Xinxin Wang, Xian Zhang, Chun Chou, Briana G. Nixon, Kristelle J. Capistrano, Min Peng, A. Efeyan, D. Sabatini, Ming O. Li
{"title":"Nutrient mTORC1 signaling underpins regulatory T cell control of immune tolerance","authors":"Mytrang H Do, Xinxin Wang, Xian Zhang, Chun Chou, Briana G. Nixon, Kristelle J. Capistrano, Min Peng, A. Efeyan, D. Sabatini, Ming O. Li","doi":"10.1084/jem.20190848","DOIUrl":"https://doi.org/10.1084/jem.20190848","url":null,"abstract":"Rag GTPase–dependent nutrient mTORC1 signaling plays a critical role in control of T reg cell suppression of autoimmunity and tumor immunity. These findings establish nutrients as a novel class of signaling molecule.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"107 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77414617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 24
Histone methyltransferase Nsd2 is required for follicular helper T cell differentiation 组蛋白甲基转移酶Nsd2是滤泡辅助性T细胞分化所必需的
The Tokushima journal of experimental medicine Pub Date : 2019-10-21 DOI: 10.1084/jem.20190832
Xuehui Long, Le Zhang, Yang Zhang, Min Min, Bichun Lin, Jingjing Chen, Xiaojie Ma, Sulan Zhai, Zhenming Cai, Yingxia Liu, Yanlai Lu, N. Che, W. Tan, J. Qin, Xiaoming Wang
{"title":"Histone methyltransferase Nsd2 is required for follicular helper T cell differentiation","authors":"Xuehui Long, Le Zhang, Yang Zhang, Min Min, Bichun Lin, Jingjing Chen, Xiaojie Ma, Sulan Zhai, Zhenming Cai, Yingxia Liu, Yanlai Lu, N. Che, W. Tan, J. Qin, Xiaoming Wang","doi":"10.1084/jem.20190832","DOIUrl":"https://doi.org/10.1084/jem.20190832","url":null,"abstract":"Regulation of Bcl6 expression during follicular helper T cell differentiation remains incompletely understood. Here, Long et al. show that T cell activation induces H3K36me2 methyltransferase Nsd2, in a CD28- and ICOS-dependent manner, to promote Bcl6 expression and Tfh differentiation.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86711120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 16
GM-CSF in inflammation 炎症中的GM-CSF
The Tokushima journal of experimental medicine Pub Date : 2019-10-14 DOI: 10.1084/jem.20190945
J. Hamilton
{"title":"GM-CSF in inflammation","authors":"J. Hamilton","doi":"10.1084/jem.20190945","DOIUrl":"https://doi.org/10.1084/jem.20190945","url":null,"abstract":"GM-CSF is a potential therapeutic target in inflammation and autoimmunity. This study reviews the literature on the biology of GM-CSF, in particular that describing the research leading to clinical trials targeting GM-CSF and its receptor in numerous inflammatory/autoimmune conditions, such as rheumatoid arthritis.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78590807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 152
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