Although many chronic inflammatory diseases share the feature of elevated IL-17 production, therapeutic targeting of IL-17 has vastly different clinical outcomes. Here the authors summarize the recent progress in understanding the protective and pathogenic role of the IL-23/IL-17 axis in preclinical models and human inflammatory diseases.
{"title":"Targeting interleukin-17 in chronic inflammatory disease: A clinical perspective","authors":"P. Zwicky, S. Unger, B. Becher","doi":"10.1084/jem.20191123","DOIUrl":"https://doi.org/10.1084/jem.20191123","url":null,"abstract":"Although many chronic inflammatory diseases share the feature of elevated IL-17 production, therapeutic targeting of IL-17 has vastly different clinical outcomes. Here the authors summarize the recent progress in understanding the protective and pathogenic role of the IL-23/IL-17 axis in preclinical models and human inflammatory diseases.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"217 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86986746","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}
Xingrong Du, H. Zeng, Shaofeng Liu, C. Guy, Yogesh Dhungana, G. Neale, M. Bergo, H. Chi
Thymocyte egress is a critical determinant of T cell homeostasis and adaptive immunity. Du et al. describe unexpected roles of mevalonate metabolism–fueled protein geranylgeranylation, but not farnesylation, in driving thymocyte egress through modulating Cdc42 and Pak activities.
{"title":"Mevalonate metabolism–dependent protein geranylgeranylation regulates thymocyte egress","authors":"Xingrong Du, H. Zeng, Shaofeng Liu, C. Guy, Yogesh Dhungana, G. Neale, M. Bergo, H. Chi","doi":"10.1084/jem.20190969","DOIUrl":"https://doi.org/10.1084/jem.20190969","url":null,"abstract":"Thymocyte egress is a critical determinant of T cell homeostasis and adaptive immunity. Du et al. describe unexpected roles of mevalonate metabolism–fueled protein geranylgeranylation, but not farnesylation, in driving thymocyte egress through modulating Cdc42 and Pak activities.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87255288","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}
A. Tanaka, H. Nishikawa, Shinsuke Noguchi, D. Sugiyama, Hiromasa Morikawa, Yoshiko Takeuchi, D. Ha, Naoya Shigeta, T. Kitawaki, Y. Maeda, Takuro Saito, Yoshinori Shinohara, Y. Kameoka, K. Iwaisako, F. Monma, K. Ohishi, J. Karbach, E. Jäger, K. Sawada, N. Katayama, N. Takahashi, S. Sakaguchi
As a novel type of anticancer reagent, imatinib inhibits not only BCR-ABL oncogenic protein but also LCK in T cells as an off-target, being able to selectively deplete mature T reg cells and thereby evoke effective immune responses to various cancers.
{"title":"Tyrosine kinase inhibitor imatinib augments tumor immunity by depleting effector regulatory T cells","authors":"A. Tanaka, H. Nishikawa, Shinsuke Noguchi, D. Sugiyama, Hiromasa Morikawa, Yoshiko Takeuchi, D. Ha, Naoya Shigeta, T. Kitawaki, Y. Maeda, Takuro Saito, Yoshinori Shinohara, Y. Kameoka, K. Iwaisako, F. Monma, K. Ohishi, J. Karbach, E. Jäger, K. Sawada, N. Katayama, N. Takahashi, S. Sakaguchi","doi":"10.1084/jem.20191009","DOIUrl":"https://doi.org/10.1084/jem.20191009","url":null,"abstract":"As a novel type of anticancer reagent, imatinib inhibits not only BCR-ABL oncogenic protein but also LCK in T cells as an off-target, being able to selectively deplete mature T reg cells and thereby evoke effective immune responses to various cancers.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79815893","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}
Zhen Xiong, P. Xia, Xiaoxiao Zhu, Jingjing Geng, Shuo Wang, B. Ye, Xiwen Qin, Yuan Qu, Luyun He, Dongdong Fan, Ying Du, Yong Tian, Z. Fan
Xiong et al. show that CCP3 performs deglutamylation of BAP1 to stabilize BAP1, which eliminates H2AK119Ub from Hoxa1 promoter and initiates Hoxa1 expression, leading to enhanced HSC self-renewal.
{"title":"Glutamylation of deubiquitinase BAP1 controls self-renewal of hematopoietic stem cells and hematopoiesis","authors":"Zhen Xiong, P. Xia, Xiaoxiao Zhu, Jingjing Geng, Shuo Wang, B. Ye, Xiwen Qin, Yuan Qu, Luyun He, Dongdong Fan, Ying Du, Yong Tian, Z. Fan","doi":"10.1084/jem.20190974","DOIUrl":"https://doi.org/10.1084/jem.20190974","url":null,"abstract":"Xiong et al. show that CCP3 performs deglutamylation of BAP1 to stabilize BAP1, which eliminates H2AK119Ub from Hoxa1 promoter and initiates Hoxa1 expression, leading to enhanced HSC self-renewal.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"169 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86640986","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}
Jennifer K. Bando, S. Gilfillan, B. Di Luccia, J. L. Fachi, Cristiane Sécca, M. Cella, M. Colonna
This study shows that the regulatory innate lymphoid cell (ILCreg), a recently described IL-10–producing innate lymphocyte, is not present in mice bred in four different facilities. Instead, group 2 ILCs provide an inducible source of IL-10 in the intestine.
{"title":"ILC2s are the predominant source of intestinal ILC-derived IL-10","authors":"Jennifer K. Bando, S. Gilfillan, B. Di Luccia, J. L. Fachi, Cristiane Sécca, M. Cella, M. Colonna","doi":"10.1084/jem.20191520","DOIUrl":"https://doi.org/10.1084/jem.20191520","url":null,"abstract":"This study shows that the regulatory innate lymphoid cell (ILCreg), a recently described IL-10–producing innate lymphocyte, is not present in mice bred in four different facilities. Instead, group 2 ILCs provide an inducible source of IL-10 in the intestine.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73830756","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}
Xiuxiu Liu, Lin Yang, Ling-Xiao Shao, Yang He, Gang Wu, Y. Bao, Nan-nan Lu, Dong-Mei Gong, Yangyang Lu, Tian-Tian Cui, Ninghe Sun, Dan-yang Chen, W. Shi, K. Fukunaga, Hong-Shan Chen, Zhong Chen, Feng Han, Ying-Mei Lu
Liu et al. reveal a key mechanism that mediating the transition from cerebrovascular damage to epilepsy. They identify the endothelial cyclin-dependent kinase 5 (CDK5) regulates astrocytic glutamate reuptake and increased glutamate synaptic function through CXCL1/CXCR2-mediated astrogliosis.
{"title":"Endothelial Cdk5 deficit leads to the development of spontaneous epilepsy through CXCL1/CXCR2-mediated reactive astrogliosis","authors":"Xiuxiu Liu, Lin Yang, Ling-Xiao Shao, Yang He, Gang Wu, Y. Bao, Nan-nan Lu, Dong-Mei Gong, Yangyang Lu, Tian-Tian Cui, Ninghe Sun, Dan-yang Chen, W. Shi, K. Fukunaga, Hong-Shan Chen, Zhong Chen, Feng Han, Ying-Mei Lu","doi":"10.1084/jem.20180992","DOIUrl":"https://doi.org/10.1084/jem.20180992","url":null,"abstract":"Liu et al. reveal a key mechanism that mediating the transition from cerebrovascular damage to epilepsy. They identify the endothelial cyclin-dependent kinase 5 (CDK5) regulates astrocytic glutamate reuptake and increased glutamate synaptic function through CXCL1/CXCR2-mediated astrogliosis.","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78339048","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}
Alvin Pratama, Alexandra Schnell, D. Mathis, C. Benoist
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.
{"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}
Dehong Yan, Jing-Horng Wang, Honghong Sun, Aliyeh Zamani, Hongling Zhang, Weihong Chen, A. Tang, Qingguo Ruan, Xiaolu Yang, Youhai H. Chen, X. Wan
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.
{"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}
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
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.
{"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}
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
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.
{"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}
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