Journal of Experimental Medicine最新文献_第9页

Women in STEM becoming independent: Our shared motivation and enthusiasm are our driving force. 科技、工程和数学领域的女性正在独立：我们共同的动力和热情是我们前进的动力。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-08-05 Epub Date: 2024-06-24 DOI: 10.1084/jem.20240971

Liudmila Andreeva, Lidia Bosurgi, Shu Zhen Chong, Coco Chu, Yejing Ge, Esther Hoste, Kellie A Jurado, Jette Lengefeld, Archita Mishra, Stefanie Wculek, Arabella Young

引用次数: 0

STAT3 gain of function: Too much of a good thing in the skin! STAT3 功能增强：皮肤中的好东西太多了！

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-08-05 Epub Date: 2024-07-01 DOI: 10.1084/jem.20240849

Cindy S Ma, Stuart G Tangye

引用次数: 0

Send it, receive it, quick erase it: A mouse model to decipher chemokine communication. 发送、接收、快速删除：解读趋化因子通讯的小鼠模型

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-07-01 Epub Date: 2024-05-07 DOI: 10.1084/jem.20240582

Leen Hermans, Timothy E O'Sullivan

引用次数: 0

Patients and mice with deficiency in the SNARE protein SYNTAXIN-11 have a secondary B cell defect. 缺乏 SNARE 蛋白 SYNTAXIN-11 的患者和小鼠会出现继发性 B 细胞缺陷。

IF 15.3 1区医学

Journal of Experimental Medicine Pub Date : 2024-07-01 Epub Date: 2024-05-09 DOI: 10.1084/jem.20221122

Tamara Kögl, Hsin-Fang Chang, Julian Staniek, Samuel C C Chiang, Gudrun Thoulass, Jessica Lao, Kristoffer Weißert, Viviane Dettmer-Monaco, Kerstin Geiger, Paul T Manna, Vivien Beziat, Mana Momenilandi, Szu-Min Tu, Selina J Keppler, Varsha Pattu, Philipp Wolf, Laurence Kupferschmid, Stefan Tholen, Laura E Covill, Karolina Ebert, Tobias Straub, Miriam Groß, Ruth Gather, Helena Engel, Ulrich Salzer, Christoph Schell, Sarah Maier, Kai Lehmberg, Tatjana I Cornu, Hanspeter Pircher, Mohammad Shahrooei, Nima Parvaneh, Roland Elling, Marta Rizzi, Yenan T Bryceson, Stephan Ehl, Peter Aichele, Sandra Ammann

{"title":"Patients and mice with deficiency in the SNARE protein SYNTAXIN-11 have a secondary B cell defect.","authors":"Tamara Kögl, Hsin-Fang Chang, Julian Staniek, Samuel C C Chiang, Gudrun Thoulass, Jessica Lao, Kristoffer Weißert, Viviane Dettmer-Monaco, Kerstin Geiger, Paul T Manna, Vivien Beziat, Mana Momenilandi, Szu-Min Tu, Selina J Keppler, Varsha Pattu, Philipp Wolf, Laurence Kupferschmid, Stefan Tholen, Laura E Covill, Karolina Ebert, Tobias Straub, Miriam Groß, Ruth Gather, Helena Engel, Ulrich Salzer, Christoph Schell, Sarah Maier, Kai Lehmberg, Tatjana I Cornu, Hanspeter Pircher, Mohammad Shahrooei, Nima Parvaneh, Roland Elling, Marta Rizzi, Yenan T Bryceson, Stephan Ehl, Peter Aichele, Sandra Ammann","doi":"10.1084/jem.20221122","DOIUrl":"10.1084/jem.20221122","url":null,"abstract":"SYNTAXIN-11 (STX11) is a SNARE protein that mediates the fusion of cytotoxic granules with the plasma membrane at the immunological synapses of CD8 T or NK cells. Autosomal recessive inheritance of deleterious STX11 variants impairs cytotoxic granule exocytosis, causing familial hemophagocytic lymphohistiocytosis type 4 (FHL-4). In several FHL-4 patients, we also observed hypogammaglobulinemia, elevated frequencies of naive B cells, and increased double-negative DN2:DN1 B cell ratios, indicating a hitherto unrecognized role of STX11 in humoral immunity. Detailed analysis of Stx11-deficient mice revealed impaired CD4 T cell help for B cells, associated with disrupted germinal center formation, reduced isotype class switching, and low antibody avidity. Mechanistically, Stx11-/- CD4 T cells exhibit impaired membrane fusion leading to reduced CD107a and CD40L surface mobilization and diminished IL-2 and IL-10 secretion. Our findings highlight a critical role of STX11 in SNARE-mediated membrane trafficking and vesicle exocytosis in CD4 T cells, important for successful CD4 T cell-B cell interactions. Deficiency in STX11 impairs CD4 T cell-dependent B cell differentiation and humoral responses.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 7","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11082451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stress relief of chemo illness. 缓解化疗疾病的压力

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-07-01 Epub Date: 2024-05-06 DOI: 10.1084/jem.20240545

Adam J Rose, Sarah H Lockie

引用次数: 0

Correction: TET2-STAT3-CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition. 更正：TET2-STAT3-CXCL5 nexus促进中性粒细胞脂质转移，助长肺腺癌向鳞癌的转化。

IF 15.3 1区医学

Journal of Experimental Medicine Pub Date : 2024-07-01 Epub Date: 2024-06-07 DOI: 10.1084/jem.2024011106032024c

Yun Xue, Yuting Chen, Sijia Sun, Xinyuan Tong, Yujia Chen, Shijie Tang, Xue Wang, Simin Bi, Yuqin Qiu, Qiqi Zhao, Zhen Qin, Qin Xu, Yingjie Ai, Leilei Chen, Beizhen Zhang, Zhijie Liu, Minbiao Ji, Meidong Lang, Luonan Chen, Guoliang Xu, Liang Hu, Dan Ye, Hongbin Ji

引用次数: 0

Act1 drives chemoresistance via regulation of antioxidant RNA metabolism and redox homeostasis. Act1通过调节抗氧化RNA代谢和氧化还原平衡驱动化疗抗性

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-07-01 Epub Date: 2024-06-11 DOI: 10.1084/jem.20231442

Lingzi Hong, Tomasz Herjan, Xing Chen, Leah L Zagore, Katarzyna Bulek, Han Wang, Chi-Fu Jeffrey Yang, Donny D Licatalosi, Xiaoxia Li, Xiao Li

{"title":"Act1 drives chemoresistance via regulation of antioxidant RNA metabolism and redox homeostasis.","authors":"Lingzi Hong, Tomasz Herjan, Xing Chen, Leah L Zagore, Katarzyna Bulek, Han Wang, Chi-Fu Jeffrey Yang, Donny D Licatalosi, Xiaoxia Li, Xiao Li","doi":"10.1084/jem.20231442","DOIUrl":"10.1084/jem.20231442","url":null,"abstract":"The IL-17 receptor adaptor molecule Act1, an RNA-binding protein, plays a critical role in IL-17-mediated cancer progression. Here, we report a novel mechanism of how IL-17/Act1 induces chemoresistance by modulating redox homeostasis through epitranscriptomic regulation of antioxidant RNA metabolism. Transcriptome-wide mapping of direct Act1-RNA interactions revealed that Act1 binds to the 5'UTR of antioxidant mRNAs and Wilms' tumor 1-associating protein (WTAP), a key regulator in m6A methyltransferase complex. Strikingly, Act1's binding sites are located in proximity to m6A modification sites, which allows Act1 to promote the recruitment of elF3G for cap-independent translation. Loss of Act1's RNA binding activity or Wtap knockdown abolished IL-17-induced m6A modification and translation of Wtap and antioxidant mRNAs, indicating a feedforward mechanism of the Act1-WTAP loop. We then developed antisense oligonucleotides (Wtap ASO) that specifically disrupt Act1's binding to Wtap mRNA, abolishing IL-17/Act1-WTAP-mediated antioxidant protein production during chemotherapy. Wtap ASO substantially increased the antitumor efficacy of cisplatin, demonstrating a potential therapeutic strategy for chemoresistance.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 7","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I IFN pathway. PD-L1 通过抑制 I 型 IFN 途径的代谢转变促进溶瘤病毒感染。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-07-01 Epub Date: 2024-06-13 DOI: 10.1084/jem.20221721

Jonathan J Hodgins, John Abou-Hamad, Colin Edward O'Dwyer, Ash Hagerman, Edward Yakubovich, Christiano Tanese de Souza, Marie Marotel, Ariel Buchler, Saleh Fadel, Maria M Park, Claire Fong-McMaster, Mathieu F Crupi, Olivia Joan Makinson, Reem Kurdieh, Reza Rezaei, Harkirat Singh Dhillon, Carolina S Ilkow, John C Bell, Mary-Ellen Harper, Benjamin H Rotstein, Rebecca C Auer, Barbara C Vanderhyden, Luc A Sabourin, Marie-Claude Bourgeois-Daigneault, David P Cook, Michele Ardolino

{"title":"PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I IFN pathway.","authors":"Jonathan J Hodgins, John Abou-Hamad, Colin Edward O'Dwyer, Ash Hagerman, Edward Yakubovich, Christiano Tanese de Souza, Marie Marotel, Ariel Buchler, Saleh Fadel, Maria M Park, Claire Fong-McMaster, Mathieu F Crupi, Olivia Joan Makinson, Reem Kurdieh, Reza Rezaei, Harkirat Singh Dhillon, Carolina S Ilkow, John C Bell, Mary-Ellen Harper, Benjamin H Rotstein, Rebecca C Auer, Barbara C Vanderhyden, Luc A Sabourin, Marie-Claude Bourgeois-Daigneault, David P Cook, Michele Ardolino","doi":"10.1084/jem.20221721","DOIUrl":"10.1084/jem.20221721","url":null,"abstract":"While conventional wisdom initially postulated that PD-L1 serves as the inert ligand for PD-1, an emerging body of literature suggests that PD-L1 has cell-intrinsic functions in immune and cancer cells. In line with these studies, here we show that engagement of PD-L1 via cellular ligands or agonistic antibodies, including those used in the clinic, potently inhibits the type I interferon pathway in cancer cells. Hampered type I interferon responses in PD-L1-expressing cancer cells resulted in enhanced efficacy of oncolytic viruses in vitro and in vivo. Consistently, PD-L1 expression marked tumor explants from cancer patients that were best infected by oncolytic viruses. Mechanistically, PD-L1 promoted a metabolic shift characterized by enhanced glycolysis rate that resulted in increased lactate production. In turn, lactate inhibited type I IFN responses. In addition to adding mechanistic insight into PD-L1 intrinsic function, our results will also help guide the numerous ongoing efforts to combine PD-L1 antibodies with oncolytic virotherapy in clinical trials.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 7","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11176258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

γδ T cell profiling in a cohort of preterm infants reveals elevated frequencies of CD83+ γδ T cells in sepsis. 早产儿组群中的γδ T 细胞图谱显示，败血症中 CD83+ γδ T 细胞频率升高。

IF 2.9 1区医学

Journal of Experimental Medicine Pub Date : 2024-07-01 Epub Date: 2024-05-16 DOI: 10.1084/jem.20231987

Ximena León-Lara, Alina S Fichtner, Maike Willers, Tao Yang, Katharina Schaper, Lennart Riemann, Jennifer Schöning, Anna Harms, Vicente Almeida, Anja Schimrock, Anika Janssen, Laura Ospina-Quintero, Constantin von Kaisenberg, Reinhold Förster, Matthias Eberl, Manuela F Richter, Sabine Pirr, Dorothee Viemann, Sarina Ravens

{"title":"γδ T cell profiling in a cohort of preterm infants reveals elevated frequencies of CD83+ γδ T cells in sepsis.","authors":"Ximena León-Lara, Alina S Fichtner, Maike Willers, Tao Yang, Katharina Schaper, Lennart Riemann, Jennifer Schöning, Anna Harms, Vicente Almeida, Anja Schimrock, Anika Janssen, Laura Ospina-Quintero, Constantin von Kaisenberg, Reinhold Förster, Matthias Eberl, Manuela F Richter, Sabine Pirr, Dorothee Viemann, Sarina Ravens","doi":"10.1084/jem.20231987","DOIUrl":"10.1084/jem.20231987","url":null,"abstract":"Preterm infants are at high risk of developing neonatal sepsis. γδ T cells are thought to be an important set of effector cells in neonates. Here, γδ T cells were investigated in a longitudinal cohort of preterm neonates using next-generation sequencing, flow cytometry, and functional assays. During the first year of life, the Vγ9Vδ2 T cell subset showed dynamic phenotypic changes and elevated levels of fetal-derived Vγ9Vδ2 T cells were evident in infants with sepsis. Single-cell transcriptomics identified HLA-DRhiCD83+ γδ T cells in neonatal sepsis, which expressed genes related to antigen presentation. In vitro assays showed that CD83 was expressed on activated Vγ9Vδ2 T cells in preterm and term neonates, but not in adults. In contrast, activation of adult Vγ9Vδ2 T cells enhanced CD86 expression, which was presumably the key receptor to induce CD4 T cell proliferation. Together, we provide a map of the maturation of γδ T cells after preterm birth and highlight their phenotypic diversity in infections.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11098939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Women in STEM becoming independent: The journey to independence is an immensely gratifying odyssey. 科技、工程和数学领域的女性开始独立：通往独立的旅程是令人无比欣喜的奥德赛。

IF 15.3 1区医学

Journal of Experimental Medicine Pub Date : 2024-07-01 Epub Date: 2024-06-11 DOI: 10.1084/jem.20240842

Clarissa Campbell, Maja C Funk, Yuki Hattori, Wei Hu, Jana Jeschke, Colleen M Lau, Guang Sheng Ling, Siqi Liu, Verónica Lloréns-Rico, Elisa Nemes

引用次数: 0