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VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours 期刊论文
NATURE, 2020, 577 (7792) : 689-+
作者:  Toll, Velle;  Christensen, Matthew;  Quaas, Johannes;  Bellouin, Nicolas
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

In a mouse model of glioblastoma, treatment with VEGF-C increases lymphatic drainage in the central nervous system and improves the immune response, suggesting that modulating meningeal lymphatics could enhance checkpoint inhibitor therapy.


Immune surveillance against pathogens and tumours in the central nervous system is thought to be limited owing to the lack of lymphatic drainage. However, the characterization of the meningeal lymphatic network has shed light on previously unappreciated ways that an immune response can be elicited to antigens that are expressed in the brain(1-3). Despite progress in our understanding of the development and structure of the meningeal lymphatic system, the contribution of this network in evoking a protective antigen-specific immune response in the brain remains unclear. Here, using a mouse model of glioblastoma, we show that the meningeal lymphatic vasculature can be manipulated to mount better immune responses against brain tumours. The immunity that is mediated by CD8 T cells to the glioblastoma antigen is very limited when the tumour is confined to the central nervous system, resulting in uncontrolled tumour growth. However, ectopic expression of vascular endothelial growth factor C (VEGF-C) promotes enhanced priming of CD8 T cells in the draining deep cervical lymph nodes, migration of CD8 T cells into the tumour, rapid clearance of the glioblastoma and a long-lasting antitumour memory response. Furthermore, transfection of an mRNA construct that expresses VEGF-C works synergistically with checkpoint blockade therapy to eradicate existing glioblastoma. These results reveal the capacity of VEGF-C to promote immune surveillance of tumours, and suggest a new therapeutic approach to treat brain tumours.


  
Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells 期刊论文
NATURE, 2020, 577 (7792) : 676-+
作者:  Zhao, Ruozhu;  Chen, Xin;  Ma, Weiwei;  Zhang, Jinyu;  Guo, Jie;  Zhong, Xiu;  Yao, Jiacheng;  Sun, Jiahui;  Rubinfien, Julian;  Zhou, Xuyu;  Wang, Jianbin;  Qi, Hai
收藏  |  浏览/下载:12/0  |  提交时间:2020/07/03

Empirical and anecdotal evidence has associated stress with accelerated hair greying (formation of unpigmented hairs)(1,2), but so far there has been little scientific validation of this link. Here we report that, in mice, acute stress leads to hair greying through the fast depletion of melanocyte stem cells. Using a combination of adrenalectomy, denervation, chemogenetics(3,4), cell ablation and knockout of the adrenergic receptor specifically in melanocyte stem cells, we find that the stress-induced loss of melanocyte stem cells is independent of immune attack or adrenal stress hormones. Instead, hair greying results from activation of the sympathetic nerves that innervate the melanocyte stem-cell niche. Under conditions of stress, the activation of these sympathetic nerves leads to burst release of the neurotransmitter noradrenaline (also known as norepinephrine). This causes quiescent melanocyte stem cells to proliferate rapidly, and is followed by their differentiation, migration and permanent depletion from the niche. Transient suppression of the proliferation of melanocyte stem cells prevents stress-induced hair greying. Our study demonstrates that neuronal activity that is induced by acute stress can drive a rapid and permanent loss of somatic stem cells, and illustrates an example in which the maintenance of somatic stem cells is directly influenced by the overall physiological state of the organism.


Stress induces hair greying in mice through depletion of melanocyte stem cells, which is mediated by the activation of sympathetic nerves rather than through immune attack or adrenal stress hormones.


  
Late Upper Paleolithic occupation at Cooper's Ferry, Idaho, USA, similar to 16,000 years ago 期刊论文
SCIENCE, 2019, 365 (6456) : 891-+
作者:  Davis, Loren G.;  Madsen, David B.;  Becerra-Valdivia, Lorena;  Higham, Thomas;  Sisson, David A.;  Skinner, Sarah M.;  Stueber, Daniel;  Nyers, Alexander J.;  Keen-Zebert, Amanda;  Neudorf, Christina;  Cheyney, Melissa;  Izuho, Masami;  Iizuka, Fumie;  Burns, Samuel R.;  Epps, Clinton W.;  Willis, Samuel C.;  Buvit, Ian
收藏  |  浏览/下载:17/0  |  提交时间:2019/11/27
PLANETARY SCIENCE The origin of Saturn's rings and moons 期刊论文
SCIENCE, 2019, 364 (6445) : 1028-1030
作者:  Ida, Shigeru
收藏  |  浏览/下载:6/0  |  提交时间:2019/11/27
Woody vegetation dynamics in the tropical and subtropical Andes from 2001 to 2014: Satellite image interpretation and expert validation 期刊论文
GLOBAL CHANGE BIOLOGY, 2019, 25 (6) : 2112-2126
作者:  Mitchell Aide, T.;  Ricardo Grau, H.;  Graesser, Jordan;  Jose Andrade-Nunez, Maria;  Araoz, Ezequiel;  Barros, Ana P.;  Campos-Cerqueira, Marconi;  Chacon-Moreno, Eulogio;  Cuesta, Francisco;  Espinoza, Raul;  Peralvo, Manuel;  Polk, Molly H.;  Rueda, Ximena;  Sanchez, Adriana;  Young, Kenneth R.;  Zarba, Lucia;  Zimmerer, Karl S.
收藏  |  浏览/下载:14/0  |  提交时间:2019/11/26
agriculture  coupled natural human systems  expert validation  forest loss and regeneration  MODIS satellite imagery  
Supracellular contractions propel migration 期刊论文
SCIENCE, 2018, 362 (6412) : 290-291
作者:  Adameyko, Igor
收藏  |  浏览/下载:11/0  |  提交时间:2019/11/27
The Gift of Global Talent How Migration Shapes Business, Economy & Society 期刊论文
SCIENCE, 2018, 362 (6412) : 296-296
作者:  Shih, Kevin
收藏  |  浏览/下载:4/0  |  提交时间:2019/11/27
Orchestrating cortical brain development 期刊论文
SCIENCE, 2018, 361 (6404) : 754-+
作者:  Thomas, Jean-Leon
收藏  |  浏览/下载:4/0  |  提交时间:2019/11/27
The search for ancient DNA heads east 期刊论文
SCIENCE, 2018, 361 (6397) : 31-32
作者:  Bellwood, Peter
收藏  |  浏览/下载:0/0  |  提交时间:2019/11/27
Policy distortions, farm size, and the overuse of agricultural chemicals in China 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (27) : 7010-7015
作者:  Wu, Yiyun;  Xi, Xican;  Tang, Xin;  Luo, Deming;  Gu, Baojing;  Lam, Shu Kee;  Vitousek, Peter M.;  Chen, Deli
收藏  |  浏览/下载:9/0  |  提交时间:2019/11/27
crop yield  environmental protection  fertilizer use efficiency  socioeconomic barriers  urbanization