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The human fetal thymus generates invariant effector γδ T cells 人胎儿胸腺产生不变的效应γδ T细胞
Pub Date : 2019-12-05 DOI: 10.1084/jem.20190580
Paola Tieppo, M. Papadopoulou, Deborah Gatti, N. McGovern, J. Chan, F. Gosselin, Glenn Goetgeluk, K. Weening, Ling Ma, N. Dauby, Alexandra Cogan, C. Donner, F. Ginhoux, B. Vandekerckhove, D. Vermijlen
Tieppo et al. show that the human fetal thymus generates invariant γδ T cells with programmed effector functions. This is due to an intrinsic property of fetal HSPCs caused by high expression of the RNA-binding protein Lin28b.
Tieppo等人表明,人类胎儿胸腺产生具有程序化效应功能的不变γδ T细胞。这是由于高表达rna结合蛋白Lin28b引起的胎儿造血干细胞的固有特性。
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引用次数: 54
Loss of IL-10 signaling in macrophages limits bacterial killing driven by prostaglandin E2 巨噬细胞中IL-10信号的丢失限制了前列腺素E2驱动的细菌杀伤
Pub Date : 2019-12-05 DOI: 10.1084/jem.20180649
S. Mukhopadhyay, E. Heinz, I. Porreca, K. Alasoo, Amy T. Y. Yeung, Huei-Ting Yang, T. Schwerd, J. Forbester, C. Hale, Chukwuma A. Agu, Yoon Ha Choi, Julia Rodrigues, M. Capitani, L. Jostins-Dean, D. Thomas, S. Travis, Daniel J. Gaffney, W. Skarnes, N. Thomson, H. Uhlig, G. Dougan, F. Powrie
Cytokines and lipid mediators are key regulators of inflammation; but how they are mechanistically linked is poorly understood. Here, Mukhopadhyay et al. show a novel regulation between cytokine IL-10 and lipid mediator PGE2 that functionally connects them to intestinal inflammation.
细胞因子和脂质介质是炎症的关键调节因子;但人们对它们之间的机械联系知之甚少。在这里,Mukhopadhyay等人展示了细胞因子IL-10和脂质介质PGE2之间的一种新的调节,在功能上将它们与肠道炎症联系起来。
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引用次数: 41
LncRNA-encoded polypeptide ASRPS inhibits triple-negative breast cancer angiogenesis lncrna编码的多肽ASRPS抑制三阴性乳腺癌血管生成
Pub Date : 2019-12-05 DOI: 10.1084/jem.20190950
Yirong Wang, Siqi Wu, Xun Zhu, Liyuan Zhang, Jieqiong Deng, Fang Li, Binbin Guo, Sheng-hua Zhang, Rui Wu, Zheng Zhang, Kexin Wang, Jiachun Lu, Yifeng Zhou
In this study, Wang et al. demonstrate that lncRNA-encoded polypeptide ASRPS is down-regulated in TNBC. ASRPS regulates angiogenesis and may serve as a novel prognostic marker and therapeutic target for TNBC.
在本研究中,Wang等人证实lncrna编码的多肽ASRPS在TNBC中下调。ASRPS调节血管生成,可能作为TNBC新的预后标志物和治疗靶点。
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引用次数: 122
Intratumoral delivery of RIG-I agonist SLR14 induces robust antitumor responses. RIG-I 激动剂 SLR14 的瘤内给药可诱导强有力的抗肿瘤反应。
Pub Date : 2019-12-02 Epub Date: 2019-10-10 DOI: 10.1084/jem.20190801
Xiaodong Jiang, Viswanathan Muthusamy, Olga Fedorova, Yong Kong, Daniel J Kim, Marcus Bosenberg, Anna Marie Pyle, Akiko Iwasaki

Cytosolic nucleic acid-sensing pathways can be triggered to enhance immune response to cancer. In this study, we tested the antitumor activity of a unique RIG-I agonist, stem loop RNA (SLR) 14. In the immunogenic tumor models, we observed significant tumor growth delay and an extended survival in SLR14-treated mice. SLR14 also greatly improved antitumor efficacy of anti-PD1 antibody over single-agent treatment. SLR14 was mainly taken up by CD11b+ myeloid cells in the tumor microenvironment, and many genes associated with immune defense were significantly up-regulated after treatment, accompanied by increase in the number of CD8+ T lymphocytes, NK cells, and CD11b+ cells in SLR14-treated tumors. Strikingly, SLR14 dramatically inhibited nonimmunogenic B16 tumor growth, and the cured mice developed an immune memory. Furthermore, a systemic antitumor response was observed in both bilateral and tumor metastasis models. Collectively, our results demonstrate that SLR14 is a promising therapeutic RIG-I agonist for cancer treatment, either alone or in combination with existing immunotherapies.

细胞质核酸感应通路可被触发,以增强对癌症的免疫反应。在这项研究中,我们测试了一种独特的 RIG-I 激动剂--茎环 RNA (SLR) 14 的抗肿瘤活性。在免疫原性肿瘤模型中,我们观察到经 SLR14 处理的小鼠肿瘤生长明显延迟,存活期延长。与单药治疗相比,SLR14 还大大提高了抗 PD1 抗体的抗肿瘤疗效。SLR14主要被肿瘤微环境中的CD11b+髓系细胞吸收,许多与免疫防御相关的基因在治疗后显著上调,同时SLR14治疗的肿瘤中CD8+T淋巴细胞、NK细胞和CD11b+细胞的数量也有所增加。引人注目的是,SLR14 显著抑制了非免疫原性 B16 肿瘤的生长,而且治愈的小鼠产生了免疫记忆。此外,在双侧和肿瘤转移模型中都观察到了全身性抗肿瘤反应。总之,我们的研究结果表明,SLR14 是一种很有前途的治疗性 RIG-I 激动剂,可单独或与现有的免疫疗法结合使用,用于癌症治疗。
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引用次数: 43
A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function. 一种因 CDC42 功能异常而导致的涉及造血功能障碍、炎症和 HLH 的新型疾病。
Pub Date : 2019-12-02 Epub Date: 2019-10-10 DOI: 10.1084/jem.20190147
Michael T Lam, Simona Coppola, Oliver H F Krumbach, Giusi Prencipe, Antonella Insalaco, Cristina Cifaldi, Immacolata Brigida, Erika Zara, Serena Scala, Silvia Di Cesare, Simone Martinelli, Martina Di Rocco, Antonia Pascarella, Marcello Niceta, Francesca Pantaleoni, Andrea Ciolfi, Petra Netter, Alexandre F Carisey, Michael Diehl, Mohammad Akbarzadeh, Francesca Conti, Pietro Merli, Anna Pastore, Stefano Levi Mortera, Serena Camerini, Luciapia Farina, Marcel Buchholzer, Luca Pannone, Tram N Cao, Zeynep H Coban-Akdemir, Shalini N Jhangiani, Donna M Muzny, Richard A Gibbs, Luca Basso-Ricci, Maria Chiriaco, Radovan Dvorsky, Lorenza Putignani, Rita Carsetti, Petra Janning, Asbjorg Stray-Pedersen, Hans Christian Erichsen, AnnaCarin Horne, Yenan T Bryceson, Lamberto Torralba-Raga, Kim Ramme, Vittorio Rosti, Claudia Bracaglia, Virginia Messia, Paolo Palma, Andrea Finocchi, Franco Locatelli, Ivan K Chinn, James R Lupski, Emily M Mace, Caterina Cancrini, Alessandro Aiuti, Mohammad R Ahmadian, Jordan S Orange, Fabrizio De Benedetti, Marco Tartaglia

Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. Patients shared the same de novo CDC42 mutation (Chr1:22417990C>T, p.R186C) and altered hematopoietic compartment, immune dysregulation, and inflammation. CDC42 mutations had been associated with syndromic neurodevelopmental disorders. In vitro and in vivo assays documented unique effects of p.R186C on CDC42 localization and function, correlating with the distinctiveness of the trait. Emapalumab was critical to the survival of one patient, who underwent successful bone marrow transplantation. Early recognition of the disorder and establishment of treatment followed by bone marrow transplant are important to survival.

嗜血细胞性淋巴组织细胞增多症(HLH)的特点是由于过度激活的免疫细胞未得到充分抑制而导致免疫失调,其临床表现多种多样,与更常见的病理生理有重叠之处。HLH 难以诊断,而且可能是炎症综合征的一部分。在这里,我们在四名无亲属关系的患者中发现了一种新型血液病/自身炎症(NOCARH 综合征),该综合征具有可叠加的特征,包括新生儿期发病的全血细胞减少伴造血功能障碍、自身炎症、皮疹和 HLH。患者具有相同的 CDC42 基因突变(Chr1:22417990C>T, p.R186C)和造血区系改变、免疫失调和炎症。CDC42 突变与综合神经发育障碍有关。体外和体内试验记录了p.R186C对CDC42定位和功能的独特影响,这与该性状的独特性相关。埃马帕鲁单抗对一名患者的存活至关重要,该患者成功进行了骨髓移植。及早发现这种疾病并确定治疗方案,然后进行骨髓移植对患者的存活非常重要。
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引用次数: 0
Mechanism of differential Zika and dengue virus neutralization by a public antibody lineage targeting the DIII lateral ridge 针对DIII侧脊的公共抗体谱系对寨卡病毒和登革热病毒的差异中和机制
Pub Date : 2019-11-22 DOI: 10.1084/jem.20191792
Haiyan Zhao, Lily Xu, Robin Bombardi, Rachel S. Nargi, Z. Deng, J. Errico, C. Nelson, Kimberly A. Dowd, T. Pierson, J. Crowe, M. Diamond, D. Fremont
Evaluation of the human antibody response to Zika virus has identified common germline-derived mAbs capable of cross flavivirus neutralization. Zhao et al. provide a detailed mechanistic understanding of how flavivirus infections are prevented in a strain-specific manner by a representative mAb.
对寨卡病毒人抗体反应的评估已经确定了能够交叉中和黄病毒的常见种系衍生单克隆抗体。Zhao等人提供了一个详细的机制,了解如何通过具有代表性的单克隆抗体以菌株特异性的方式预防黄病毒感染。
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引用次数: 26
Downregulation of CFIm25 amplifies dermal fibrosis through alternative polyadenylation CFIm25的下调通过选择性聚腺苷化放大皮肤纤维化
Pub Date : 2019-11-22 DOI: 10.1084/jem.20181384
Tingting Weng, Jing-Jing Huang, E. Wagner, Junsuk Ko, Minghua Wu, N. Wareing, Yu Xiang, Ning-yuan Chen, Ping Ji, Jose G. Molina, K. Volcik, Leng Han, M. Mayes, M. Blackburn, S. Assassi
This study implicates the key regulator of alternative polyadenylation, CFIm25 in dermal fibrosis and in systemic sclerosis (scleroderma) pathogenesis. CFIm25 downregulation promotes the expression of profibrotic factors, exaggerates bleomycin-induced skin fibrosis, while CFIm25 restoration attenuates skin fibrosis.
该研究揭示了真皮纤维化和系统性硬皮病发病机制中选择性聚腺苷酸化的关键调节因子CFIm25。CFIm25下调可促进促纤维化因子的表达,加重博来霉素诱导的皮肤纤维化,而CFIm25修复可减轻皮肤纤维化。
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引用次数: 21
Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine 单细胞转录组分析揭示了人类肠道不同的营养吸收功能
Pub Date : 2019-11-21 DOI: 10.1084/jem.20191130
Yalong Wang, Wanlu Song, Jilian Wang, Ting Wang, X. Xiong, Zhen Qi, W. Fu, Xuerui Yang, Ye-Guang Chen
Single-cell transcriptome analysis of epithelial cells from human ileum, colon, and rectum reveals different nutrient-absorption preferences in the small and large intestine, providing a rich resource for further characterization of human intestine cell constitution and functions.
对人回肠、结肠和直肠上皮细胞的单细胞转录组分析揭示了小肠和大肠不同的营养吸收偏好,为进一步表征人肠细胞的结构和功能提供了丰富的资源。
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引用次数: 196
B cells are sufficient to prime the dominant CD4+ Tfh response to Plasmodium infection B细胞足以启动对疟原虫感染的显性CD4+ Tfh反应
Pub Date : 2019-11-20 DOI: 10.1084/jem.20190849
E. N. Arroyo, M. Pepper
Arroyo and Pepper demonstrate that interactions with B cells, not dendritic cells, are required for the priming of the CD4+ T cell response during Plasmodium infection. This results in a Tfh-biased response as reported by others in both mice and humans.
Arroyo和Pepper证明,在疟原虫感染期间,CD4+ T细胞应答的启动需要与B细胞相互作用,而不是树突状细胞。正如其他人在小鼠和人类中报道的那样,这导致了tfh偏倚反应。
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引用次数: 29
Correction: Cytosolic PCNA interacts with p47phox and controls NADPH oxidase NOX2 activation in neutrophils 更正:细胞质内PCNA与p47phox相互作用并控制中性粒细胞中NADPH氧化酶NOX2的激活
Pub Date : 2019-11-15 DOI: 10.1084/jem.2018037111082019c
Delphine Ohayon, Alessia De Chiara, P. My-Chan Dang, N. Thieblemont, Simon M. Chatfield, V. Marzaioli, S. S. Burgener, Julie Mocek, C. Candalh, Coralie Pintard, P. Tacnet-Delorme, G. Renault, I. Lagoutte, M. Favier, Francine Walker, M. Hurtado-Nedelec, D. Desplancq, E. Weiss, C. Benarafa, D. Housset, J. Marie, P. Frachet, J. El-Benna, V. Witko-Sarsat
2900 https://doi.org/10.1084/jem.20180371 J. Exp. Med. 2019 Vol. 216 No. 12 2900 Rockefeller University Press Correction: Cytosolic PCNA interacts with p47phox and controls NADPH oxidase NOX2 activation in neutrophils Delphine Ohayon, Alessia De Chiara, Pham My-Chan Dang, Nathalie Th ieblemont, Simon Chatfi eld, Viviana Marzaioli, Sabrina Sofi a Burgener, Julie Mocek, Céline Candalh, Coralie Pintard, Pascale Tacnet-Delorme, Gilles Renault, Isabelle Lagoutte, Maryline Favier, Francine Walker, Margarita Hurtado-Nedelec, Dominique Desplancq, Etienne Weiss, Charaf Benarafa, Dominique Housset, Jean-Claude Marie, Philippe Frachet, Jamel El-Benna, and Véronique Witko-Sarsat
2900 https://doi.org/10.1084/jem.20180371 J. Exp. Med. 2019 Vol. 216 No. 12 2900洛克菲勒大学出版社更正:胞质PCNA与p47phox相互作用,控制中性细胞中NADPH氧化酶NOX2的激活。Delphine Ohayon, Alessia De Chiara, Pham My-Chan Dang, Nathalie thieblemont, Simon Chatfi field, Viviana Marzaioli, Sabrina Sofi a Burgener, Julie Mocek, csamline Candalh, Coralie Pintard, Pascale Tacnet-Delorme, Gilles Renault, Isabelle Lagoutte, Maryline Favier, Francine Walker, Margarita hurtto - nedelec, Dominique Desplancq, Etienne Weiss, Charaf Benarafa, Dominique Housset, Jean-Claude Marie,Philippe Frachet, Jamel El-Benna和v ronique Witko-Sarsat
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引用次数: 1
期刊
The Tokushima journal of experimental medicine
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