Pub Date : 2019-11-04Epub Date: 2019-10-15DOI: 10.1084/jem.20191880
Stephanie Houston
Arkaitz Carracedo is a principal investigator at the Association for Cooperative Research in Biosciences (CIC bioGUNE) in Spain; his laboratory focuses on signaling and metabolic alterations in cancer. Arkaitz has investigated the regulation of fatty acid oxidation in cancer cells and how these changes could be manipulated therapeutically. We chatted with Arkaitz to find out about his career in science so far.
{"title":"Arkaitz Carracedo: If the scientific question is good, the result will be interesting.","authors":"Stephanie Houston","doi":"10.1084/jem.20191880","DOIUrl":"10.1084/jem.20191880","url":null,"abstract":"<p><p>Arkaitz Carracedo is a principal investigator at the Association for Cooperative Research in Biosciences (CIC bioGUNE) in Spain; his laboratory focuses on signaling and metabolic alterations in cancer. Arkaitz has investigated the regulation of fatty acid oxidation in cancer cells and how these changes could be manipulated therapeutically. We chatted with Arkaitz to find out about his career in science so far.</p>","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73071354","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}
Pub Date : 2019-11-04Epub Date: 2019-08-21DOI: 10.1084/jem.20190993
Saskia Hemmers, Michail Schizas, Elham Azizi, Stanislav Dikiy, Yi Zhong, Yongqiang Feng, Grégoire Altan-Bonnet, Alexander Y Rudensky
Regulatory T (T reg) cells, a specialized subset of CD4+ T cells, are essential to prevent fatal autoimmunity. Expression of the T reg lineage-defining transcription factor Foxp3, and therefore their differentiation in the thymus, is dependent upon T cell receptor (TCR) and interleukin-2 (IL-2) signaling. Here, we report that the majority of IL-2-producing cells in the thymus are mature CD4 single-positive (CD4SP) thymocytes and that continuous IL-2 production sustained thymic T reg cell generation and control of systemic immune activation. Furthermore, single-cell RNA sequencing analysis of CD4 thymocyte subsets revealed that IL-2 was expressed in self-reactive CD4SP thymocytes, which also contain T reg precursor cells. Thus, our results suggest that the thymic T reg cell pool size is scaled by a key niche factor, IL-2, produced by self-reactive CD4SP thymocytes. This IL-2-dependent scaling of thymic T reg cell generation by overall self-reactivity of a mature post-selection thymic precursor pool may likely ensure adequate control of autoimmunity.
调节性 T（Treg）细胞是 CD4+ T 细胞的一个特殊亚群，对防止致命性自身免疫至关重要。Treg 界系转录因子 Foxp3 的表达及其在胸腺中的分化依赖于 T 细胞受体（TCR）和白细胞介素-2（IL-2）信号。在这里，我们报告了胸腺中大多数产生IL-2的细胞是成熟的CD4单阳性（CD4SP）胸腺细胞，持续产生的IL-2可维持胸腺Treg细胞的生成和对全身免疫激活的控制。此外，CD4胸腺细胞亚群的单细胞RNA测序分析表明，IL-2在自我反应性CD4SP胸腺细胞中表达，而这些细胞中也含有Treg前体细胞。因此，我们的研究结果表明，胸腺 Treg 细胞池的大小是由自我反应性 CD4SP 胸腺细胞产生的关键生态位因子 IL-2 决定的。成熟的后选胸腺前体细胞池的整体自我反应性对胸腺Treg细胞生成的这种IL-2依赖性缩放可能确保了对自身免疫的充分控制。
{"title":"IL-2 production by self-reactive CD4 thymocytes scales regulatory T cell generation in the thymus.","authors":"Saskia Hemmers, Michail Schizas, Elham Azizi, Stanislav Dikiy, Yi Zhong, Yongqiang Feng, Grégoire Altan-Bonnet, Alexander Y Rudensky","doi":"10.1084/jem.20190993","DOIUrl":"10.1084/jem.20190993","url":null,"abstract":"<p><p>Regulatory T (T reg) cells, a specialized subset of CD4<sup>+</sup> T cells, are essential to prevent fatal autoimmunity. Expression of the T reg lineage-defining transcription factor Foxp3, and therefore their differentiation in the thymus, is dependent upon T cell receptor (TCR) and interleukin-2 (IL-2) signaling. Here, we report that the majority of IL-2-producing cells in the thymus are mature CD4 single-positive (CD4SP) thymocytes and that continuous IL-2 production sustained thymic T reg cell generation and control of systemic immune activation. Furthermore, single-cell RNA sequencing analysis of CD4 thymocyte subsets revealed that IL-2 was expressed in self-reactive CD4SP thymocytes, which also contain T reg precursor cells. Thus, our results suggest that the thymic T reg cell pool size is scaled by a key niche factor, IL-2, produced by self-reactive CD4SP thymocytes. This IL-2-dependent scaling of thymic T reg cell generation by overall self-reactivity of a mature post-selection thymic precursor pool may likely ensure adequate control of autoimmunity.</p>","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73267196","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}
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":null,"pages":null},"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}
Pub Date : 2019-11-04Epub Date: 2019-08-27DOI: 10.1084/jem.20190351
Qiaoli Ma, Yann Decker, Andreas Müller, Benjamin V Ineichen, Steven T Proulx
The pathways of circulation and clearance of cerebrospinal fluid (CSF) in the spine have yet to be elucidated. We have recently shown with dynamic in vivo imaging that routes of outflow of CSF in mice occur along cranial nerves to extracranial lymphatic vessels. Here, we use near-infrared and magnetic resonance imaging to demonstrate the flow of CSF tracers within the spinal column and reveal the major spinal pathways for outflow to lymphatic vessels in mice. We found that after intraventricular injection, a spread of CSF tracers occurs within both the central canal and the spinal subarachnoid space toward the caudal end of the spine. Outflow of CSF tracers from the spinal subarachnoid space occurred predominantly from intravertebral regions of the sacral spine to lymphatic vessels, leading to sacral and iliac LNs. Clearance of CSF from the spine to lymphatic vessels may have significance for many conditions, including multiple sclerosis and spinal cord injury.
{"title":"Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels.","authors":"Qiaoli Ma, Yann Decker, Andreas Müller, Benjamin V Ineichen, Steven T Proulx","doi":"10.1084/jem.20190351","DOIUrl":"10.1084/jem.20190351","url":null,"abstract":"<p><p>The pathways of circulation and clearance of cerebrospinal fluid (CSF) in the spine have yet to be elucidated. We have recently shown with dynamic in vivo imaging that routes of outflow of CSF in mice occur along cranial nerves to extracranial lymphatic vessels. Here, we use near-infrared and magnetic resonance imaging to demonstrate the flow of CSF tracers within the spinal column and reveal the major spinal pathways for outflow to lymphatic vessels in mice. We found that after intraventricular injection, a spread of CSF tracers occurs within both the central canal and the spinal subarachnoid space toward the caudal end of the spine. Outflow of CSF tracers from the spinal subarachnoid space occurred predominantly from intravertebral regions of the sacral spine to lymphatic vessels, leading to sacral and iliac LNs. Clearance of CSF from the spine to lymphatic vessels may have significance for many conditions, including multiple sclerosis and spinal cord injury.</p>","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82021352","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}
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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}
M. Yukawa, S. Jagannathan, Sushmitha Vallabh, A. Kartashov, Xiaoting Chen, M. Weirauch, A. Barski
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.
{"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":null,"pages":null},"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}
H. Hosokawa, Maile Romero-Wolf, Qi Yang, Y. Motomura, D. Levanon, Y. Groner, K. Moro, Tomoaki Tanaka, E. Rothenberg
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.
{"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":null,"pages":null},"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}
Mytrang H Do, Xinxin Wang, Xian Zhang, Chun Chou, Briana G. Nixon, Kristelle J. Capistrano, Min Peng, A. Efeyan, D. Sabatini, Ming O. Li
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.
{"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":null,"pages":null},"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}
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