Journal of Experimental Medicine

Journal of Experimental Medicine The Journal of Experimental Medicine publishes immunology, cancer, stem cells, microbial pathogenesis, vascular biology, and neurobiology research.
The Journal of Experimental Medicine (JEM) features peer-reviewed research on immunology, cancer biology, stem cell biology, microbial pathogenesis, vascular biology, and neurobiology. All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JEM provides free online access to many article types immediately, with complete archival content freely available online. Established in 1896, JEM is published by The Rockefeller University Press. For more information, visit http://jem.rupress.org. Follow us on Twitter: https://twitter.com/JExpMed
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Since its inception in 1896, the goal of The Journal of Experimental Medicine (JEM) has been to publish outstanding and enduring studies in medical biology. At a time when many leading publishing groups are establishing topic-specific journals, we believe it is critical to complement that approach by offering a distinguished venue for publication of studies that integrate disciplines within the field of pathogenesis. A distinctive editorial system supports this goal with an emphasis on exceptional service to our authors. Two groups of editors work hand-in hand: professional editors with strong scientific backgrounds, and full-time practicing scientists. At least one editor from each group evaluates the merits of each paper prior to external review. The editors convene weekly to discuss all papers with external referee comments, and reach rapid decisions without excessive requests for revision. Within the field of medical biology we focus both on human studies and diverse in vivo experimental models of human disease that address such topics as genetics, inflammation, immunity, infectious disease, cancer, vascular biology, metabolic disorders, neuroscience, and stem cell biology. We welcome reports ranging from atomic-level analyses to clinical interventions that illustrate new mechanisms.

NKG2D is a danger sensor expressed on different subsets of innate and adaptive lymphocytes. This study by Marina Babic, ...
06/01/2020
NK cell receptor NKG2D enforces proinflammatory features and pathogenicity of Th1 and Th17 cells

NKG2D is a danger sensor expressed on different subsets of innate and adaptive lymphocytes. This study by Marina Babic, Chiara Romagnani, and colleagues (https://bit.ly/2B7w8xQ) demonstrates how NKG2D enforces proinflammatory features of Th1 and Th17 cells and promotes inflammation in vivo, identifying NKG2D as an important target for the amelioration of Th1/ Th17-mediated inflammatory diseases.

NKG2D is a danger sensor expressed on different subsets of innate and adaptive lymphocytes.

Jeffrey H. Lin, Robert H. Vonderheide, and colleagues (https://bit.ly/2XBI8PX) show that type 1 conventional dendritic c...
05/29/2020
Type 1 conventional dendritic cells are systemically dysregulated early in pancreatic carcinogenesis | Journal of Experimental Medicine | Rockefeller University Press

Jeffrey H. Lin, Robert H. Vonderheide, and colleagues (https://bit.ly/2XBI8PX) show that type 1 conventional dendritic cells are progressively and systemically dysregulated during pancreatic carcinogenesis, subject to semimaturation and IL-6–driven apoptosis. Yet, CD40 agonist synergizes with Flt3L to rescue cDC1 abundance and maturation, enabling a return to full CD8+ T cell priming.

Type 1 conventional dendritic cells (cDC1s) are typically thought to be dysregulated secondarily to invasive cancer.

Read short summaries of articles in JEM’s new immunology collection (https://bit.ly/2Ln47nN) for the #AAI2020 meeting fr...
05/28/2020
JEM Immunology Collection 2020

Read short summaries of articles in JEM’s new immunology collection (https://bit.ly/2Ln47nN) for the #AAI2020 meeting from the labs of Anita A. Koshy and Christopher A. Hunter, Thirumala-Devi Kanneganti, Stuart G. Tangye and Cindy S. Ma, Joan M. Goverman, Katherine A. Fitzgerald, Alexander Y. Rudensky, Michel C. Nussenzweig, Jean-Laurent Casanova, Jason G. Cyster, Micah D. Gearhart and Marc K. Jenkins, Sophie Hambleton, Caroline Rooryck, Kenneth G.C. Smith, and Michael J. Lenardo, Ross M. Kedl, Cullen M. Dutmer, and Elena W.Y. Hsieh, and Geoffrey T. Hart and Eric O. Long.. Download the PDF here: https://bit.ly/3bqHp8T

For over 120 years, JEM has been the venue for seminal studies in the field of immunology, from basic concepts to translational science.

Qingxin Zhou, Zhiyong Zhang, and colleagues (https://bit.ly/3gtpjHf) characterize a critical role of CLK3 on purine meta...
05/28/2020
Targeting CLK3 inhibits the progression of cholangiocarcinoma by reprogramming nucleotide metabolism

Qingxin Zhou, Zhiyong Zhang, and colleagues (https://bit.ly/3gtpjHf) characterize a critical role of CLK3 on purine metabolism in cholangiocarcinoma (CCA). Overexpressed or mutated CLK3 promotes CCA progression in vitro and in vivo. Therefore, CLK3 may serve as a biomarker and potential drug target for CCA.

CDC-like kinase 3 (CLK3) is a dual specificity kinase that functions on substrates containing serine/threonine and tyrosine.

On the cover of JEM—Xiaoyan Zhan, Jianghong Man, and colleagues demonstrate that glioma stem-like cells (GSCs) evade typ...
05/27/2020

On the cover of JEM—Xiaoyan Zhan, Jianghong Man, and colleagues demonstrate that glioma stem-like cells (GSCs) evade type-I IFN suppression through MBD3/NuRD complex–mediated STAT1 downregulation. The cover image shows expression of MBD3 (red) and STAT1 (green) is mutually exclusive in human GBM specimen. Nuclei were counterstained with Hoechst (blue). Image provided by the authors. Image © Zhan et al., 2020. https://bit.ly/3cXv1ic

We are temporarily making all articles in Journal of Experimental Medicine (JEM) free to read until June 30, 2020 while ...
05/27/2020
RUP response to COVID-19 crisis

We are temporarily making all articles in Journal of Experimental Medicine (JEM) free to read until June 30, 2020 while we explore additional ways to support remote access for researchers at home. Learn more about the steps we’re taking and find COVID-19 relevant content: https://bit.ly/2UCUhUr

Proactive measures to assist researchers.

Researchers at the University of Nebraska Medical Center have identified a key cell signaling pathway that drives the de...
05/27/2020

Researchers at the University of Nebraska Medical Center have identified a key cell signaling pathway that drives the devastating muscle loss, or cachexia, suffered by many cancer patients. The study, published in JEM (https://bit.ly/2XwSX5O), suggests that targeting this pathway with a drug already in phase 2 clinical trials for diabetes could prevent this syndrome. Read the press release here: https://bit.ly/2TGSnRH

This study by Aneesha Dasgupta, David A. Tuveson, Pankaj K. Singh, and colleagues (https://bit.ly/2XwSX5O) demonstrates ...
05/26/2020
SIRT1–NOX4 signaling axis regulates cancer cachexia

This study by Aneesha Dasgupta, David A. Tuveson, Pankaj K. Singh, and colleagues (https://bit.ly/2XwSX5O) demonstrates a novel signaling pathway regulating pancreatic cancer cachexia. These results establish that the Sirt1–Nox4 signaling axis plays an essential role in the manifestation of pancreatic cancer cachexia, and inhibition of this axis abrogates the cachexia syndrome.

Approximately one third of cancer patients die due to complexities related to cachexia. However, the mechanisms of cachexia and the potential therapeutic interventions remain poorly studied.

Francisco et al. identify that chloride intracellular channel 1 (CLIC1) is overexpressed in human central nervous system...
05/25/2020

Francisco et al. identify that chloride intracellular channel 1 (CLIC1) is overexpressed in human central nervous system malignancies, including medulloblastoma, a common pediatric brain cancer. This image shows chloride intracellular channel 1 in a brain tumor sample. Image © Francisco et al., 2020 https://bit.ly/2ZotopX

In this study, Ali Hussain, Laurie E. Ailles, and colleagues (https://bit.ly/2TohjgB) demonstrate that cancer-associated...
05/22/2020
Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21

In this study, Ali Hussain, Laurie E. Ailles, and colleagues (https://bit.ly/2TohjgB) demonstrate that cancer-associated fibroblasts (CAFs) in high-grade serous ovarian cancer are heterogeneous, that CAF state drives cancer aggressiveness and patient outcomes, and that TCF21 is a master regulator of CAF state.

Recent studies indicate that cancer-associated fibroblasts (CAFs) are phenotypically and functionally heterogeneous.

On the cover of JEM—Xiaoyan Zhan, Jianghong Man, and colleagues demonstrate that glioma stem-like cells (GSCs) evade typ...
05/21/2020

On the cover of JEM—Xiaoyan Zhan, Jianghong Man, and colleagues demonstrate that glioma stem-like cells (GSCs) evade type-I IFN suppression through MBD3/NuRD complex–mediated STAT1 downregulation. The cover image shows expression of MBD3 (red) and STAT1 (green) is mutually exclusive in human GBM specimen. Nuclei were counterstained with Hoechst (blue). Image provided by the authors. Image © Zhan et al., 2020. https://bit.ly/3cXv1ic

Sohinee Bhattacharyya, Mara Sherman, and colleagues (https://bit.ly/3e3AYdH) show that MYC is a molecular point of conve...
05/21/2020
Acidic fibroblast growth factor underlies microenvironmental regulation of MYC in pancreatic cancer

Sohinee Bhattacharyya, Mara Sherman, and colleagues (https://bit.ly/3e3AYdH) show that MYC is a molecular point of convergence for microenvironmental and cell-autonomous signals in RAS-transformed pancreatic cancer cells. They identify cancer-associated fibroblast–derived FGF1 as a critical paracrine regulator of MYC, and a novel link between the pancreatic tumor microenvironment and oncogenic transcription.

Despite a critical role for MYC as an effector of oncogenic RAS, strategies to target MYC activity in RAS-driven cancers are lacking.

JEM’s immunology collection (https://bit.ly/2Ln47nN) for the #AAI2020 meeting features advances in immunology ranging fr...
05/20/2020
JEM Immunology Collection 2020

JEM’s immunology collection (https://bit.ly/2Ln47nN) for the #AAI2020 meeting features advances in immunology ranging from fundamental concepts to human immunology and the interaction of pathogens with the host immune system. It also includes exciting reviews on the role of gasdermins in immunity and inflammation, the contribution of T cell cytokines to multiple sclerosis, and how IL-21 regulates the germinal center and humoral immunity. Download new short summaries of articles in a PDF here: https://bit.ly/3bqHp8T

For over 120 years, JEM has been the venue for seminal studies in the field of immunology, from basic concepts to translational science.

CMV is emerging as a key driver of immunosenescence. Georgina Bowyer, Katie J. Ewer, and colleagues (https://bit.ly/3g3R...
05/20/2020
Reduced Ebola vaccine responses in CMV+ young adults is associated with expansion of CD57+KLRG1+ T cells

CMV is emerging as a key driver of immunosenescence. Georgina Bowyer, Katie J. Ewer, and colleagues (https://bit.ly/3g3RCMe) report that an expansion of phenotypically senescent CD4+ and CD8+ T cells is associated with reduced responses to Ebola vaccines ChAd3–EBO-Z and MVA–EBO-Z in young UK and Senegalese adults.

CMV is associated with immunosenescence and reduced vaccine responses in the elderly (>70 yr). However, the impact of CMV in young adults is less clear. In this study, healthy UK and Senegalese adults aged 18–50 yr (average, 29 yr) were vaccinated with the Ebola vaccine candidate chimpanzee adenov...

Germinal center (GC) positively selected B cells are primarily fated for GC expansion and plasma cell formation. This st...
05/18/2020
Restriction of memory B cell differentiation at the germinal center B cell positive selection stage | Journal of Experimental Medicine | Rockefeller University Press

Germinal center (GC) positively selected B cells are primarily fated for GC expansion and plasma cell formation. This study by Amparo Toboso-Navasa, Dinis Pedro Calado, and colleagues (https://bit.ly/3cDpFst) reveals that memory B cell differentiation is restricted in positively selected B cells by the MYC–MIZ1 transcriptional repressor complex.

Memory B cells (MBCs) are key for protection from reinfection. However, it is mechanistically unclear how germinal center (GC) B cells differentiate into MBCs.

This study by Harish Palleti Janardhan, Chinmay M. Trivedi, and colleagues (https://bit.ly/3dIqnEY) demonstrates endothe...
05/15/2020
KRAS or BRAF mutations cause hepatic vascular cavernomas treatable with MAP2K–MAPK1 inhibition

This study by Harish Palleti Janardhan, Chinmay M. Trivedi, and colleagues (https://bit.ly/3dIqnEY) demonstrates endothelial KRAS or BRAF gain-of-function mutations as a causal mechanism for hepatic vascular cavernomas, the most common benign tumor of the liver. RAS-MAPK1 signaling inhibition rescues hepatic vascular cavernoma formation in endothelial KRASG12D- or BRAFV600E-expressing mice.

Human hepatic vascular cavernomas, the most common benign tumor of the liver, were described in the mid-1800s, yet the mechanisms for their formation and effective treatments remain unknown.

Kun He, Amanda C. Poholek, and colleagues (https://bit.ly/3fPyYaQ) show that the transcriptional repressor Blimp-1, know...
05/14/2020
Blimp-1 is essential for allergen-induced asthma and Th2 cell development in the lung

Kun He, Amanda C. Poholek, and colleagues (https://bit.ly/3fPyYaQ) show that the transcriptional repressor Blimp-1, known to constrain autoimmunity, is an unexpected and critical positive regulator of Th2 cells in the lung acting via an IL-10–STAT3 axis in response to inhaled allergens, driving pathophysiology associated with asthma disease.

A Th2 immune response is central to allergic airway inflammation, which afflicts millions worldwide. However, the mechanisms that augment GATA3 expression in an antigen-primed developing Th2 cell are not well understood.

Presenting a NEW special collection of immunology research articles and reviews. The collection presents recent and exci...
05/13/2020

Presenting a NEW special collection of immunology research articles and reviews. The collection presents recent and exciting advances ranging from fundamental concepts to human immunology and the interaction of pathogens with the host immune system. It also includes exciting reviews on the role of gasdermins in immunity and inflammation, the contribution of T cell cytokines to multiple sclerosis, and how IL-21 regulates the germinal center and humoral immunity: https://bit.ly/2Ln47nN

We are also pleased to present a special collection PDF that contains brief summaries of all the research articles with input from their authors. Download the special collection PDF here: https://bit.ly/3bqHp8T

Chiranjeevi Bodda, Søren R. Paludan, and colleagues (https://bit.ly/3bm9P4d) show that the deubiquitinase activity of th...
05/12/2020
HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection

Chiranjeevi Bodda, Søren R. Paludan, and colleagues (https://bit.ly/3bm9P4d) show that the deubiquitinase activity of the HSV1 VP1-2 protein inhibits induction of type I interferon in the brain. This is mediated through deubiquitination of the signaling protein STING, thus preventing activation of host defense after sensing of viral DNA by cGAS.

Herpes simplex virus (HSV) is the main cause of viral encephalitis in the Western world, and the type I interferon (IFN) system is important for antiviral control in the brain.

Research from Aarhus University, published in JEM (https://bit.ly/3bm9P4d), discovered a molecular mechanism that helps ...
05/08/2020

Research from Aarhus University, published in JEM (https://bit.ly/3bm9P4d), discovered a molecular mechanism that helps herpes simplex virus (HSV1) infect the brain. The study shows that HSV1's VP1-2 protein can deactivate the early immune response. Read the press release here: https://bit.ly/3cbzZYq

Xueli Zhang, Lydia Sorokin, and colleagues (https://bit.ly/2ytwHRU) identify a new subendothelial/basement membrane (BM)...
05/08/2020
The endothelial basement membrane acts as a checkpoint for entry of pathogenic T cells into the brain

Xueli Zhang, Lydia Sorokin, and colleagues (https://bit.ly/2ytwHRU) identify a new subendothelial/basement membrane (BM) niche in which the phenotype of CNS-infiltrating T cells is modulated by interaction with endothelial BM laminins via integrins α6β1 and αvβ1, affecting differentiation to pathogenic Th17 cells and motility.

The endothelial cell basement membrane (BM) is a barrier to migrating leukocytes and a rich source of signaling molecules that can influence extravasating cells.

Rong En Tay, Kai W. Wucherpfennig, and colleagues (https://bit.ly/3c8iKXW) show that HDAC3 acts early during CD8 T cell ...
05/07/2020
Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells

Rong En Tay, Kai W. Wucherpfennig, and colleagues (https://bit.ly/3c8iKXW) show that HDAC3 acts early during CD8 T cell activation to inhibit cytotoxicity and effector differentiation gene programs. This study identifies a novel role for HDAC3 as an epigenetic regulator of CD8 T cell cytotoxicity and persistence following activation.

Cytotoxic T cells play a key role in adaptive immunity by killing infected or cancerous cells.

Patricia M. Santos, Lisa H. Butterfield, and colleagues (https://bit.ly/3fmpGTz) analyze cancer patient vaccine antigen-...
05/06/2020
Impact of checkpoint blockade on cancer vaccine–activated CD8+ T cell responses

Patricia M. Santos, Lisa H. Butterfield, and colleagues (https://bit.ly/3fmpGTz) analyze cancer patient vaccine antigen-specific T cells for the importance of immune checkpoint molecule and gene pathway expression. CTLA-4 and PD-1 pathways are significantly correlated to T cell response and clinical outcomes, and sequence of pathway blockade is critical.

Immune and molecular profiling of CD8 T cells of patients receiving DC vaccines expressing three full-length melanoma antigens (MAs) was performed.

"Altmetric Badges provide a very early and immediate indicator in terms of what the community is saying about a piece of...
05/05/2020
Altmetric vs. Dimensions Badges: Understanding the Full Story About Research - Silverchair

"Altmetric Badges provide a very early and immediate indicator in terms of what the community is saying about a piece of research, while the Dimensions Badges tell the long-term story of more formal citations." Learn about the metric badges available on each of our articles: https://bit.ly/3cFqh08

This guest blog is written by Cathy Holland, Director, Global Publisher Business Development at Digital Science, a partner in the Silverchair Universe program. Here at Digital Science we are no stranger to Badges. The iconic graphics posted on content pages give authors, publishers, and other...

Emily C. Freund, Aditya Murthy, and colleagues (https://bit.ly/3fc5gw7) show that highly efficient gene editing in prima...
05/04/2020
Efficient gene knockout in primary human and murine myeloid cells by non-viral delivery of CRISPR-Cas9

Emily C. Freund, Aditya Murthy, and colleagues (https://bit.ly/3fc5gw7) show that highly efficient gene editing in primary myeloid cells is made possible by optimized non-viral delivery of CRISPR-Cas9. This enables single and multiplexed gene knockout in monocytes, macrophages, and dendritic cells to advance innate immunity research and cell therapy.

Myeloid cells play critical and diverse roles in mammalian physiology, including tissue development and repair, innate defense against pathogens, and generation of adaptive immunity.

The latest People & Ideas features Vijay Rathinam (https://bit.ly/3aJvRNG), Assistant Professor of Immunology and the Di...
05/01/2020
Vijay Rathinam: Cherishing the small victories

The latest People & Ideas features Vijay Rathinam (https://bit.ly/3aJvRNG), Assistant Professor of Immunology and the Director of the Graduate Program in Immunology at UConn Health. His work is focused on understanding pathogen recognition by the innate immune system, specifically how the inflammasome is activated by Gram-negative bacteria.

Our work aims at decoding fundamental mechanisms in intracellular innate immune recognition and signaling during bacterial and viral infections.

Clarifying conflicting previous reports, Jeannette L. Tenthorey, Isabella Rauch, and colleagues (https://bit.ly/2VOclvt)...
05/01/2020
NLRC4 inflammasome activation is NLRP3- and phosphorylation-independent during infection and does not protect from melanoma | Journal of Experimental Medicine | Rockefeller University Press

Clarifying conflicting previous reports, Jeannette L. Tenthorey, Isabella Rauch, and colleagues (https://bit.ly/2VOclvt) demonstrate, in vitro and in vivo, that phosphorylation of NLRC4 is neither necessary nor sufficient for NAIP/NLRC4 inflammasome activation. Further, NLRC4 plays no role in a model of melanoma.

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The Journal of Experimental Medicine (JEM) features peer-reviewed research on immunology, cancer biology, stem cell biology, microbial pathogenesis, vascular biology, and neurobiology. All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JEM provides free online access to many article types from the date of publication and to all archival content. Established in 1896, JEM is published by The Rockefeller University Press. For more information, visit http://jem.rupress.org. Follow us on Twitter: https://twitter.com/JExpMed

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