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.

A new study in JEM (https://bit.ly/2EdIJOX) shows that, by altering the gut microbiome, long-term antibiotic treatment r...
05/17/2019

A new study in JEM (https://bit.ly/2EdIJOX) shows that, by altering the gut microbiome, long-term antibiotic treatment reduces inflammation and slows the growth of amyloid plaques in the brains of male mice, though the same treatment has no effect on female animals. Read the press release here: https://bit.ly/2LPg8FL

Which antigen-presenting cells are involved in Tfh responses in humans remains unclear. Durand et al. (https://bit.ly/2v...
05/16/2019
Human lymphoid organ cDC2 and macrophages play complementary roles in T follicular helper responses

Which antigen-presenting cells are involved in Tfh responses in humans remains unclear. Durand et al. (https://bit.ly/2vY2XYw) show that human tonsil cDC2 and CD14+ macrophages provide Tfh polarizing signals to CD4+ T cells in distinct locations within tonsil, playing sequential roles in Tfh induction.

CD4+ T follicular helper (Tfh) cells are essential for inducing efficient humoral responses. T helper polarization is classically orientated by dendritic cells (DCs), which are composed of several subpopulations with distinct functions. Whether human DC...

The endoribonuclease Regnase-1 suppresses inflammation through RNA degradation. Here, Tanaka et al. (https://bit.ly/2Ekl...
05/15/2019
Phosphorylation-dependent Regnase-1 release from endoplasmic reticulum is critical in IL-17 response

The endoribonuclease Regnase-1 suppresses inflammation through RNA degradation. Here, Tanaka et al. (https://bit.ly/2Eklent) show that Regnase-1 is phosphorylated and inactivated by the Act1-TBK1-IKKi axis during IL-17 stimulation. Moreover, this phosphorylation substantially contributes to the mRNA stabilization needed for amplification of TH17-cell–mediated inflammation.

Regnase-1 (also known as Zc3h12a or MCPIP-1) is an endoribonuclease involved in mRNA degradation of inflammation-associated genes. Regnase-1 is inactivated in response to external stimuli through post-translational modifications including phosphorylatio...

Fritz and Lenardo (https://bit.ly/2W36OBZ) discuss the basic science and clinical discoveries of immune checkpoint block...
05/14/2019
Development of immune checkpoint therapy for cancer

Fritz and Lenardo (https://bit.ly/2W36OBZ) discuss the basic science and clinical discoveries of immune checkpoint blockade, which boosts antitumor immunity and increases survival of patients with cancer.

Since the early 20th century, immunologists have investigated mechanisms that protect vertebrates from damaging immune responses against self-antigens by mature lymphocytes, i.e., peripheral tolerance. These mechanisms have been increasingly delineated ...

Th17 cells provide a protective immunity against extracellular bacterial and fungal pathogens. Kotov et al. (https://bit...
05/13/2019
BCL6 corepressor contributes to Th17 cell formation by inhibiting Th17 fate suppressors

Th17 cells provide a protective immunity against extracellular bacterial and fungal pathogens. Kotov et al. (https://bit.ly/2LyJAj5) identify and characterize a mechanism by which BCOR promotes Th17 formation after Streptococcus pyogenes infection by repressing genes that inhibit the Th17 lineage.

CD4+ T helper 17 (Th17) cells protect vertebrate hosts from extracellular pathogens at mucosal surfaces. Th17 cells form from naive precursors when signals from the T cell antigen receptor (TCR) and certain cytokine receptors induce the expression of th...

Our latest issue features new research on atherosclerosis, CAR T cell activity, melanoma progression markers, glioblasto...
05/10/2019

Our latest issue features new research on atherosclerosis, CAR T cell activity, melanoma progression markers, glioblastoma, lupus pregnancy, and more: https://bit.ly/2YkAQ1t

Tiwari et al. (https://bit.ly/2YhgrKS) identify metabolically activated macrophages in obese mammary adipose tissue as a...
05/10/2019
Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer

Tiwari et al. (https://bit.ly/2YhgrKS) identify metabolically activated macrophages in obese mammary adipose tissue as an important source of IL-6, which fuels triple-negative breast cancer stemness and tumorigenesis through GP130 signaling. These mechanistic insights provide potential targets for treating obesity-associated triple-negative breast cancer.

Obesity is associated with increased incidence and severity of triple-negative breast cancer (TNBC); however, mechanisms underlying this relationship are incompletely understood. Here, we show that obesity reprograms mammary adipose tissue macrophages t...

Zhang et al. (https://bit.ly/2WwGJsd) show that clotting factors made by resident peritoneal macrophages promote microbi...
05/09/2019
Expression of factor V by resident macrophages boosts host defense in the peritoneal cavity

Zhang et al. (https://bit.ly/2WwGJsd) show that clotting factors made by resident peritoneal macrophages promote microbial trapping in fluid microenvironments where microbes might otherwise escape.

Macrophages resident in different organs express distinct genes, but understanding how this diversity fits into tissue-specific features is limited. Here, we show that selective expression of coagulation factor V (FV) by resident peritoneal macrophages ...

On the cover of JEM—Broggi et al. (https://bit.ly/2VMUZ2W) show that lymphatic exudate is highly enriched intumor-asso...
05/09/2019

On the cover of JEM—Broggi et al. (https://bit.ly/2VMUZ2W) show that lymphatic exudate is highly enriched intumor-associated factors and is therefore a promising source for biomarker discovery. The cover image represents a lymphatic vessel (green, VE-cadherin; blue, podoplanin) taking up tumor-derived extracellular vesicles (pink) after intradermal injection into the mouse ear dermis. Image credit: Léa Maillat, University of Chicago.

On the cover of JEM—Broggi et al. (https://bit.ly/2VMUZ2W) show that lymphatic exudate is highly enriched intumor-asso...
05/08/2019

On the cover of JEM—Broggi et al. (https://bit.ly/2VMUZ2W) show that lymphatic exudate is highly enriched intumor-associated factors and is therefore a promising source for biomarker discovery. The cover image represents a lymphatic vessel (green, VE-cadherin; blue, podoplanin) taking up tumor-derived extracellular vesicles (pink) after intradermal injection into the mouse ear dermis. Image credit: Léa Maillat, University of Chicago.

This JEM special collection (https://bit.ly/2vPKOf3) exhibits recent and exciting advances in immunology, celebrating ou...
05/08/2019
JEM Immunology Collection 2019

This JEM special collection (https://bit.ly/2vPKOf3) exhibits recent and exciting advances in immunology, celebrating our commitment to publishing outstanding basic immunology as well as innovative studies at the intersection of immunology with other fields such as neuroscience, cancer, and metabolism.

The Journal of Experimental Medicine (JEM) has been publishing exceptional and enduring studies for over 120 years. Many of these seminal studies have helped to define the field of immunology and progress it to the forefront of science, where major progress is being made in the development of new th...

Fernandez et al. (https://bit.ly/2DQ2pbg) show that a novel homozygous mutation in human IL2RB results in decreased IL-2...
05/07/2019
A novel human IL2RB mutation results in T and NK cell–driven immune dysregulation

Fernandez et al. (https://bit.ly/2DQ2pbg) show that a novel homozygous mutation in human IL2RB results in decreased IL-2Rβ protein expression and dysregulated IL-2/15 signaling. This hypomorphic mutation leads to decreased regulatory T cell frequency and an abnormal NK cell compartment, with clinical manifestations of autoimmunity and susceptibility to CMV.

The pleiotropic actions of interleukin-2 (IL-2) are essential for regulation of immune responses and maintenance of immune tolerance. The IL-2 receptor (IL-2R) is composed of IL-2Rα, IL-2Rβ, and IL-2Rγ subunits, with defects in IL-2Rα and IL-2Rγ and the...

Zhang et al. (https://bit.ly/2VHq2Nz) identify human IL-2Rβ deficiency as a cause of severe immune dysregulation. The h...
05/06/2019
Human interleukin-2 receptor β mutations associated with defects in immunity and peripheral tolerance

Zhang et al. (https://bit.ly/2VHq2Nz) identify human IL-2Rβ deficiency as a cause of severe immune dysregulation. The hypomorphic gene mutations reveal variable IL-2Rβ expression and function between different lymphocyte subsets as a means of selectively modulating immune responses.

Interleukin-2, which conveys essential signals for immunity, operates through a heterotrimeric receptor. Here we identify human interleukin-2 receptor (IL-2R) β chain ( IL2RB ) gene defects as a cause of life-threatening immune dysregulation. We report ...

Panicker et al. (https://bit.ly/2GS24GR) show that Fyn kinase mediates aggregated α-synuclein (αSyn) uptake as well as...
05/03/2019
Fyn kinase regulates misfolded α-synuclein uptake and NLRP3 inflammasome activation in microglia

Panicker et al. (https://bit.ly/2GS24GR) show that Fyn kinase mediates aggregated α-synuclein (αSyn) uptake as well as αSyn-mediated proinflammatory signaling in microglia, leading to NLRP3 inflammasome activation and neuroinflammation in Parkinson’s disease.

Persistent microglia-mediated neuroinflammation is a major pathophysiological contributor to the progression of Parkinson’s disease (PD), but the cell-signaling mechanisms governing chronic neuroinflammation are not well understood. Here, we show that F...

With over 40 clinical trials underway, we are nearing the first FDA approved live microbial therapeutic. Here, Jimenez, ...
05/02/2019
Microbial therapeutics: New opportunities for drug delivery

With over 40 clinical trials underway, we are nearing the first FDA approved live microbial therapeutic. Here, Jimenez, Langer and Traverso (https://bit.ly/2WdBNZ7) discuss the significant challenges of reliably administering live microorganisms to patients and the opportunities for drug delivery of these new complex therapeutics.

With >40 clinical trials underway, we are nearing the first FDA-approved live microbial therapeutic. Here, Giovanni Traverso, MIT and Harvard Medical School Assistant Professor, and colleagues Miguel Jimenez and Institute Professor Robert Langer from MI...

Congratulations to Marco Colonna and Adolfo Garcia-Sastre on their election to the National Academy of Sciences https://...
05/01/2019

Congratulations to Marco Colonna and Adolfo Garcia-Sastre on their election to the National Academy of Sciences https://bit.ly/2Lg6agv

This review by Birgit Ritter and Florian Greten (https://bit.ly/2Wh9fxJ) provides a concise overview of pro- and anti-in...
05/01/2019
Modulating inflammation for cancer therapy

This review by Birgit Ritter and Florian Greten (https://bit.ly/2Wh9fxJ) provides a concise overview of pro- and anti-inflammatory approaches in current tumor therapy.

A link between chronic inflammation and development of tumors is well established. Moreover, it has become evident that tumorigenesis is not a cell autonomous disease, and an inflammatory microenvironment is a prerequisite of basically all tumors, inclu...

Jia et al. (https://bit.ly/2DuCxkX) demonstrate that lamin B1 acts as a tumor suppressor in lung cancer. Lamin B1 loss p...
05/01/2019
Lamin B1 loss promotes lung cancer development and metastasis by epigenetic derepression of RET

Jia et al. (https://bit.ly/2DuCxkX) demonstrate that lamin B1 acts as a tumor suppressor in lung cancer. Lamin B1 loss promotes lung cancer development and metastasis by loss of PRC2 recruitment to chromatin and activation of the RET/p38 signaling axis.

Although abnormal nuclear structure is an important criterion for cancer diagnostics, remarkably little is known about its relationship to tumor development. Here we report that loss of lamin B1, a determinant of nuclear architecture, plays a key role i...

Ning et al. (https://bit.ly/2vlUJcn) find that transcription factor Hes1 acts as a homeostatic negative regulator of typ...
04/30/2019
Hes1 attenuates type I IFN responses via VEGF-C and WDFY1

Ning et al. (https://bit.ly/2vlUJcn) find that transcription factor Hes1 acts as a homeostatic negative regulator of type I interferon production to restrain interferon-mediated immune responses, including antiviral immunity and autoimmune conditions. Mechanistically, Hes1 suppresses interferon expression by targeting a regulatory circuit composed of WDFY1 and VEGF-C.

Induction of type I interferons (IFNs) is critical for eliciting competent immune responses, especially antiviral immunity. However, uncontrolled IFN production contributes to pathogenesis of autoimmune and inflammatory diseases. We found that transcrip...

Men are more likely to develop hepatocellular carcinoma (HCC) than women, but it is not clear why. In this issue of JEM,...
04/29/2019
Gender disparity in HCC: Is it the fat and not the sex?

Men are more likely to develop hepatocellular carcinoma (HCC) than women, but it is not clear why. In this issue of JEM, Manieri et al. (https://bit.ly/2GFwEDT) identify reduced adiponectin levels as responsible for the increased incidence of HCC in males.

Tim F. Greten provides insights on new research showing that adiponectin accounts for gender disparity in HCC.

Medina et al. (https://bit.ly/2W4qDG2) demonstrate that Kit oncogene activity in gastrointestinal stromal tumor modulate...
04/26/2019
Oncogenic kinase inhibition limits Batf3-dependent dendritic cell development and antitumor immunity

Medina et al. (https://bit.ly/2W4qDG2) demonstrate that Kit oncogene activity in gastrointestinal stromal tumor modulates the CD103+CD11b− dendritic cell (DC) lineage. The antitumor efficacy of oncogene inhibition initially depends on preexisting immunity orchestrated by CD103+CD11b− DCs, but subsequently is limited by a decrease in DC lineage maturation.

Gastrointestinal stromal tumor (GIST) is driven by an activating mutation in the KIT proto-oncogene. Using a mouse model of GIST and human specimens, we show that intratumoral murine CD103+CD11b− dendritic cells (DCs) and human CD141+ DCs are associated...

"I have a long-standing interest in understanding allergy pathogenesis. For many years, this has focused on the study of...
04/25/2019
Stephanie Eisenbarth: Discovering the bigger picture

"I have a long-standing interest in understanding allergy pathogenesis. For many years, this has focused on the study of allergic airway disease. More recently, some members of my laboratory and I have embarked on establishing a new direction for the laboratory focused on understanding such processes in the gut mediating food allergy." —Stephanie Eisenbarth

Stephanie Eisenbarth is an Associate Professor in the Immunology Faculty at Yale University. Her work has shown that the NOD-like receptor NLRP10 plays a role in the migration of a specific dendritic cell subset, and that when NLRP10 is missing, some de...

García-Silva et al. (https://bit.ly/2IBqp5Y) show for the first time that extracellular vesicles isolated from the exud...
04/25/2019
Use of extracellular vesicles from lymphatic drainage as surrogate markers of melanoma progression and BRAFV600E mutation

García-Silva et al. (https://bit.ly/2IBqp5Y) show for the first time that extracellular vesicles isolated from the exudative seroma obtained from the lymphatic drainage implanted in melanoma patients after lymphadenectomy can be interrogated for melanoma markers and BRAF mutations. Profiling the BRAFV600E mutation in this biofluid is a novel approach to predict disease relapse.

Liquid biopsies from cancer patients have the potential to improve diagnosis and prognosis. The assessment of surrogate markers of tumor progression in circulating extracellular vesicles could be a powerful non-invasive approach in this setting. We have...

Perinatal T cells broadly access nonlymphoid tissues, where they are exposed to sessile tissue antigens. Here, Tuncel et...
04/24/2019
T cell anergy in perinatal mice is promoted by T reg cells and prevented by IL-33

Perinatal T cells broadly access nonlymphoid tissues, where they are exposed to sessile tissue antigens. Here, Tuncel et al. (https://bit.ly/2XiVdMg) demonstrate that the availability of Foxp3+ regulatory T cells and IL-33 determine the outcome of such encounters.

Perinatal T cells broadly access nonlymphoid tissues, where they are exposed to sessile tissue antigens. To probe the outcome of such encounters, we examined the defective elimination of self-reactive clones in Aire-deficient mice. Nonlymphoid tissues w...

Hart et al. (https://bit.ly/2XbfDqq) report that Plasmodium falciparum–infected individuals in a malaria-endemic regio...
04/23/2019
Adaptive NK cells in people exposed to Plasmodium falciparum correlate with protection from malaria

Hart et al. (https://bit.ly/2XbfDqq) report that Plasmodium falciparum–infected individuals in a malaria-endemic region have an abundance of adaptive NK cells that correlates with resistance to malaria. Adaptive NK cells dominate antibody-dependent responses to P. falciparum–infected red blood cells and may contribute to acquired immunity to malaria.

How antibodies naturally acquired during Plasmodium falciparum infection provide clinical immunity to blood-stage malaria is unclear. We studied the function of natural killer (NK) cells in people living in a malaria-endemic region of Mali. Multi-parame...

Hartweger et al. (https://bit.ly/2VBGXxA) show that B cells edited by CRISPR/Cas9 to express anti–HIV-1 antibodies par...
04/22/2019
HIV-specific humoral immune responses by CRISPR/Cas9-edited B cells

Hartweger et al. (https://bit.ly/2VBGXxA) show that B cells edited by CRISPR/Cas9 to express anti–HIV-1 antibodies participate in humoral immune reactions after immunization and secrete neutralizing serum titers of anti-HIV antibodies in vivo.

A small number of HIV-1–infected individuals develop broadly neutralizing antibodies to the virus (bNAbs). These antibodies are protective against infection in animal models. However, they only emerge 1–3 yr after infection, and show a number of highly ...

García-Silva et al. (https://bit.ly/2IuLMFh) show for the first time that extracellular vesicles isolated from the exud...
04/19/2019
Use of extracellular vesicles from lymphatic drainage as surrogate markers of melanoma progression and BRAFV600E mutation

García-Silva et al. (https://bit.ly/2IuLMFh) show for the first time that extracellular vesicles isolated from the exudative seroma obtained from the lymphatic drainage implanted in melanoma patients after lymphadenectomy can be interrogated for melanoma markers and BRAF mutations. Profiling the BRAFV600E mutation in this biofluid is a novel approach to predict disease relapse.

Liquid biopsies from cancer patients have the potential to improve diagnosis and prognosis. The assessment of surrogate markers of tumor progression in circulating extracellular vesicles could be a powerful non-invasive approach in this setting. We have...

Timothy Niewold and Shilpi Mehta-Lee (https://bit.ly/2VE3sCh) provide insights on a new study from Hong et al. (https://...
04/18/2019
When pregnancy tames the wolf

Timothy Niewold and Shilpi Mehta-Lee (https://bit.ly/2VE3sCh) provide insights on a new study from Hong et al. (https://bit.ly/2VyIULg) that performed blood immunomonitoring in pregnancy, in both healthy women and women with lupus, and observed early and sustained transcriptional modulation of lupus-related pathways in both groups.

A state of relative immunosuppression exists in normal pregnancy. In this issue of JEM , Hong et al. () perform blood immunomonitoring in pregnancy, in both healthy women and women with lupus, and observe early and ...

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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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