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.
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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 immediately, with complete archival content freel

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 freel

This study from Anna-Lena Neehus, Anne Puel, Jacinta Bustamante (The Rockefeller University) and colleagues describes a ...
07/15/2021

This study from Anna-Lena Neehus, Anne Puel, Jacinta Bustamante (The Rockefeller University) and colleagues describes a decreased production of reactive oxygen species by phagocytes of PKCδ-deficient patients as a possible mechanism by which inherited human PKCδ deficiency contributes to susceptibility to infectious diseases.

This study from Anna-Lena Neehus, Anne Puel, Jacinta Bustamante (The Rockefeller University) and colleagues describes a decreased production of reactive oxygen species by phagocytes of PKCδ-deficient patients as a possible mechanism by which inherited human PKCδ deficiency contributes to susceptibility to infectious diseases.

Andrea-Hermina Györfi, Alexandru-Emil Matei, Jörg H.W Distler and colleagues (FAU Germany) show that Engrailed 1 (EN1) i...
07/14/2021
Engrailed 1 coordinates cytoskeletal reorganization to induce myofibroblast differentiation | Journal of Experimental Medicine | Rockefeller University Press

Andrea-Hermina Györfi, Alexandru-Emil Matei, Jörg H.W Distler and colleagues (FAU Germany) show that Engrailed 1 (EN1) is a key mediator of TGFβ-induced myofibroblast differentiation and fibrotic tissue remodeling. Mechanistically, EN1 induces a profibrotic gene expression profile by modulating the activity of SP transcription factors to coordinate the microtubule-stress fiber cytoskeletal rearrangements required for fibroblast activation in a ROCK-dependent manner.

This work shows that Engrailed 1 (EN1) is a key mediator of TGFβ-induced myofibroblast differentiation and fibrotic tissue remodeling. Mechanistically, EN1 indu

Duancheng Guo, Yi Zhao, Zeng-jie Yang (Fox Chase Cancer Center) and colleagues show that tumor cells can generate their ...
07/13/2021
Tumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse | Journal of Experimental Medicine | Rockefeller University Press

Duancheng Guo, Yi Zhao, Zeng-jie Yang (Fox Chase Cancer Center) and colleagues show that tumor cells can generate their supporting cells-astrocytes to facilitate tumor recurrence in medulloblastoma.

BMP-Sox9 signaling drives tumor cells to transdifferentiate into astrocytes, which contributes to the recurrence of SHH-driven medulloblastoma, a common type of

To accompany the Lysophospholipid and Related Mediators Conference (Federation of American Societies for Experimental Bi...
07/13/2021
Lipid Mediators in Immunity | Journal of Experimental Medicine | Rockefeller University Press

To accompany the Lysophospholipid and Related Mediators Conference (Federation of American Societies for Experimental Biology - FASEB), JEM is pleased to present a special collection of recent articles that uncover the roles of lysophospholipids & other signaling lipids in immunity, from modulating B cell & T cell function to mediating pathogen recognition.

We hope you enjoy the collection and and encourage your feedback!

Lipid molecules represent major structural elements of the cell as well as fuel reserves. However, lipids are also signaling molecules able to affect immune cell activity and even trigger cell death. In this special collection, we present recent JEM art...

Yu-Wen Cheng, Ze-Bei Zhang, Cheng-Chao Ruan et al. (Shanghai Institute of Hypertension) uncover a new interaction patter...
07/08/2021
PDGF-D activation by macrophage-derived uPA promotes AngII-induced cardiac remodeling in obese mice | Journal of Experimental Medicine | Rockefeller University Press

Yu-Wen Cheng, Ze-Bei Zhang, Cheng-Chao Ruan et al. (Shanghai Institute of Hypertension) uncover a new interaction pattern between macrophage and adipocyte: that macrophage-derived uPA activates adipocyte-secreted PDGF-D, which finally accelerates AngII-induced cardiac remodeling in obese mice. Targeting the uPA/PDGF-D pathway might be a potential therapeutic tool for prevention of hypertensive cardiac injury during obesity.

The authors uncover a new interaction pattern between macrophage and adipocyte: that macrophage-derived uPA activates adipocyte-secreted PDGF-D, which finally a

On the cover of our July issue: the antigen-presenting molecule CD1a (white) binds long chain sphingomyelin (blue), whic...
07/05/2021

On the cover of our July issue: the antigen-presenting molecule CD1a (white) binds long chain sphingomyelin (blue), which protrudes to the CD1a surface and blocks the approach of T cell receptors (orange and pink). This original image was made by Dr. Erica Tandori, who is an artist in residence at Monash University. She has worked together with Marcin Wegrecki and Jamie Rossjohn to generate an image that captures the main message of the paper by Cotton et al. (https://bit.ly/3fvY8vG).
Read JEM July Issue: https://bit.ly/3jou3BG

On the cover of our July issue: the antigen-presenting molecule CD1a (white) binds long chain sphingomyelin (blue), which protrudes to the CD1a surface and blocks the approach of T cell receptors (orange and pink). This original image was made by Dr. Erica Tandori, who is an artist in residence at Monash University. She has worked together with Marcin Wegrecki and Jamie Rossjohn to generate an image that captures the main message of the paper by Cotton et al. (https://bit.ly/3fvY8vG).
Read JEM July Issue: https://bit.ly/3jou3BG

Hiroyuki Hosokawa, Ellen V. Rothenberg (Caltech) and colleagues show that repression of Spi1 encoding PU.1 is crucial fo...
06/28/2021
Stage-specific action of Runx1 and GATA3 controls silencing of PU.1 expression in mouse pro–T cells | Journal of Experimental Medicine | Rockefeller University Press

Hiroyuki Hosokawa, Ellen V. Rothenberg (Caltech) and colleagues show that repression of Spi1 encoding PU.1 is crucial for early T-cell lineage commitment and depends on GATA3 and Runx1. Stage-specific Runx1 and GATA3 binding during commitment identifies a closed intronic site of mouse Spi1 that substantially contributes to Spi1 repression.

Repression of Spi1 encoding PU.1 is crucial for early T cell lineage commitment and depends on GATA3 and Runx1. Stage-specific Runx1 and GATA3 binding during co

Both normal cells and tumors release vesicles replete with proteins, DNA, RNA and other cargo, which mediate cellular cr...
06/28/2021
Extracellular vesicle– and particle-mediated communication shapes innate and adaptive immune responses | Journal of Experimental Medicine | Rockefeller University Press

Both normal cells and tumors release vesicles replete with proteins, DNA, RNA and other cargo, which mediate cellular crosstalk. However, little is known about the cargo and function of immune cell-derived extracellular vesicles. This review from Pelissier Vatter, Matei, Lyden et al. (Weill Cornell Medicine) provides an overview of the roles played by immune cell-secreted vesicles in normal physiology and disease.

While tumor-derived extracellular vesicles and particles (EVPs) are well characterized, little is known about the cargo and function of immune cell–derived EVPs

Kurt B. Pruner and Marion Pepper (University of Washington) provide a timely literature review detailing the critical, h...
06/24/2021
Local memory CD4 T cell niches in respiratory viral infection | Journal of Experimental Medicine | Rockefeller University Press

Kurt B. Pruner and Marion Pepper (University of Washington) provide a timely literature review detailing the critical, heterogeneous functions of lung resident CD4 memory T cells during respiratory viral infection. Implications for vaccine design and protection from heterologous influenza and SARS-CoV-2 reinfection are discussed.

Pruner and Pepper provide a timely literature review detailing the critical, heterogenous functions of lung resident CD4 memory T cells during respiratory viral

This study by Rui Yang, Jean-Laurent Casanova (The Rockefeller University) and colleagues describes the multiple facets ...
06/23/2021
High Th2 cytokine levels and upper airway inflammation in human inherited T-bet deficiency | Journal of Experimental Medicine | Rockefeller University Press

This study by Rui Yang, Jean-Laurent Casanova (The Rockefeller University) and colleagues describes the multiple facets and molecular basis of excessive TH2 cytokine production by CD4+ αβ T lymphocytes as a possible mechanism underlying persistent upper airway inflammation and blood eosinophilia in a patient with inherited complete T-bet deficiency.

This study describes the multiple facets and molecular basis of excessive Th2 cytokine production by CD4+ αβ T lymphocytes as a possible mechanism underlying pe

Whether and how m6A modifications regulate NK cell immunity remain unknown. Shoubao Ma, Jiazhuo Yan, Jianhua Yu (City of...
06/23/2021
The RNA m6A reader YTHDF2 controls NK cell antitumor and antiviral immunity | Journal of Experimental Medicine | Rockefeller University Press

Whether and how m6A modifications regulate NK cell immunity remain unknown. Shoubao Ma, Jiazhuo Yan, Jianhua Yu (City of Hope) and colleagues show that NK cell proliferation, survival, and effector functions are positively controlled by the RNA m6A reader YTHDF2.

Whether and how m6A modifications regulate NK cell immunity remain unknown. Here, Ma et al. show that NK cell proliferation, survival, and effector functions ar

To coincide with #ISSCR2021, we are pleased to present this special collection of recently published articles highlighti...
06/23/2021
Stem Cell Collection 2021 | Journal of Experimental Medicine | Rockefeller University Press

To coincide with #ISSCR2021, we are pleased to present this special collection of recently published articles highlighting the latest discoveries related to #StemCell research. We hope you enjoy reading this collection, and encourage your feedback!

JEM is pleased to present this special collection of recently published articles highlighting the latest discoveries related to stem cell research. Articles featured in the collection were published within the past 12 months and include original finding...

GSAP plays an important role in Alzheimer's disease, but the underlying cellular and molecular pathways remain unclear. ...
06/22/2021
GSAP regulates lipid homeostasis and mitochondrial function associated with Alzheimer's disease | Journal of Experimental Medicine | Rockefeller University Press

GSAP plays an important role in Alzheimer's disease, but the underlying cellular and molecular pathways remain unclear. Using unbiased multi-omics approaches, Peng Xu (The Rockefeller University), Jerry Chang, Yue-Ming Li and colleagues demonstrate that GSAP regulates lipid homeostasis in mitochondria-associated membranes (MAM), which affects mitochondrial function associated with the disease.

GSAP plays an important role in Alzheimer's disease, but the underlying cellular and molecular pathways remain unclear. Using unbiased multi-omics approaches, t

Ke Li, Yuexiang Wang and colleagues (Chinese Academy of Sciences) demonstrate that recurrent inactivating mutations in t...
06/21/2021
E3 ligase MKRN3 is a tumor suppressor regulating PABPC1 ubiquitination in non–small cell lung cancer | Journal of Experimental Medicine | Rockefeller University Press

Ke Li, Yuexiang Wang and colleagues (Chinese Academy of Sciences) demonstrate that recurrent inactivating mutations in the central precocious puberty-associated gene MKRN3 lead to lung cancer proliferation and progression through PABPC1 ubiquitination-mediated global protein synthesis. MKRN3 is a bona fide tumor suppressor, and MKRN3-PABPC1 deregulation represents a key pathway in NSCLC oncogenesis.

Recurrent inactivated mutations in central precocious puberty-associated gene MKRN3 lead to lung cancer proliferation and progression through PABPC1 ubiquitinat

Most patients with autosomal dominant hyper-IgE syndrome (AD-HIES) are heterozygous for rare STAT3 variants. The mechani...
06/21/2021
Human STAT3 variants underlie autosomal dominant hyper-IgE syndrome by negative dominance | Journal of Experimental Medicine | Rockefeller University Press

Most patients with autosomal dominant hyper-IgE syndrome (AD-HIES) are heterozygous for rare STAT3 variants. The mechanism of dominance was recently questioned. Takaki Asano, Bertrand Boisson, Jean-Laurent Casanova (The Rockefeller University) and colleagues show that both in-frame and out-of-frame STAT3 variants underlie AD-HIES by negative dominance and not haploinsufficiency.

Most patients with autosomal dominant hyper-IgE syndrome (AD-HIES) are heterozygous for rare STAT3 variants. The mechanism of dominance was recently questioned.

Moujtaba Y. Kasmani and Weiguo Cui (Medical College of Wisconsin) provide insights into work by Milner et al. (https://b...
06/18/2021
Inhibiting BRD4 to generate BETter T cell memory | Journal of Experimental Medicine | Rockefeller University Press

Moujtaba Y. Kasmani and Weiguo Cui (Medical College of Wisconsin) provide insights into work by Milner et al. (https://bit.ly/3xoaDRm) that shows that BRD4 plays a critical role in the effector function of CD8 T cells responding to infection and cancer.

BRD4 is a bromodomain-containing protein that binds acetylated histones to regulate transcription. In this issue of JEM, Milner et al. show that BRD4 plays a cr

This study from Lindsay M. Milich, James S. Choi Jae K. Lee et al. (The Miami Project to Cure Paralysis & The Buoniconti...
06/18/2021
Single-cell analysis of the cellular heterogeneity and interactions in the injured mouse spinal cord | Journal of Experimental Medicine | Rockefeller University Press

This study from Lindsay M. Milich, James S. Choi Jae K. Lee et al. (The Miami Project to Cure Paralysis & The Buoniconti Fund to Cure Paralysis) uses single-cell RNA sequencing to investigate the transcriptional heterogeneity of all cell types known to comprise the acutely injured spinal cord in mice. The authors investigate both cell subtype heterogeneity and potential signaling interactions between myeloid, vascular, and macroglia cells.

This study uses single-cell RNA sequencing to investigate the transcriptional heterogeneity of all cell types known to comprise the acutely injured spinal cord

Cells constantly sense their environment to adapt their behavior to changing needs. Kull and Schroeder (ETH Zürich) disc...
06/17/2021
Analyzing signaling activity and function in hematopoietic cells | Journal of Experimental Medicine | Rockefeller University Press

Cells constantly sense their environment to adapt their behavior to changing needs. Kull and Schroeder (ETH Zürich) discuss the requirements, potential, and limitations of current technologies for quantification and manipulation of cellular signaling in the context of inflammatory signaling in hematopoietic cells.

Cells constantly sense their environment to adapt their behavior to changing needs. Kull and Schroeder discuss the requirements, potential, and limitations of c

Inflammation can activate hematopoietic stem and progenitor cells (HSPC) to proliferate and differentiate, signal the sp...
06/17/2021
Inflammatory signaling regulates hematopoietic stem and progenitor cell development and homeostasis | Journal of Experimental Medicine | Rockefeller University Press

Inflammation can activate hematopoietic stem and progenitor cells (HSPC) to proliferate and differentiate, signal the specification of HSPCs during embryonic development, and maintain adult HSPC homeostasis. Amélie Collins et al. (Columbia University Irving Medical Center) review the role of inflammatory signaling in these diverse hematopoietic scenarios.

Inflammation can activate hematopoietic stem and progenitor cells (HSPCs) to proliferate and differentiate, signal the specification of HSPCs during embryonic d

Dysregulation of innate immune and inflammatory-related pathways is implicated in hematopoietic defects associated with ...
06/16/2021
Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS | Journal of Experimental Medicine | Rockefeller University Press

Dysregulation of innate immune and inflammatory-related pathways is implicated in hematopoietic defects associated with aging, clonal hematopoiesis, and MDS. Jennifer J. Trowbridge and Daniel T. Starczynowski review the current state of this field and emerging concepts that reveal critical biology and novel therapeutic opportunities.

Dysregulation of innate immune- and inflammatory-related pathways is implicated in hematopoietic defects associated with aging, clonal hematopoiesis, and MDS. W

This review from Caiado, Pietras and Manz summarizes and integrates current views on the contribution of inflammatory si...
06/16/2021
Inflammation as a regulator of hematopoietic stem cell function in disease, aging, and clonal selection | Journal of Experimental Medicine | Rockefeller University Press

This review from Caiado, Pietras and Manz summarizes and integrates current views on the contribution of inflammatory signals derived from multiple sources to hematopoietic stem cell function and its long-term implications on mutational selection and clonal expansion during aging.

This review summarizes and integrates current views on the contribution of inflammatory signals derived from multiple sources to hematopoietic stem cell functio

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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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