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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 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

X. Tao, R. Zhang, R. Du, T. Yu, Y. Shen (Tianjin Medical University) and colleagues show that activation of E-prostanoid...
04/15/2022
EP3 enhances adhesion and cytotoxicity of NK cells toward hepatic stellate cells in a murine liver fibrosis model

X. Tao, R. Zhang, R. Du, T. Yu, Y. Shen (Tianjin Medical University) and colleagues show that activation of E-prostanoid 3 receptor (EP3) ameliorates injury-induced liver fibrosis through promoting NK cell adhesion and killing of activated hepatic stellate cells in mice, indicating that EP3 may serve as a potential therapeutic target for liver fibrosis.

Tao et al. describe that activation of E-prostanoid 3 receptor (EP3) ameliorates injury-induced liver fibrosis through promoting NK cell adhesion and killing of

Moriah J. Castleman, Raul M. Torres and colleagues (University of Colorado Anschutz Medical Campus) show that BND cells ...
04/14/2022
SARS-CoV-2 infection relaxes peripheral B cell tolerance | Journal of Experimental Medicine | Rockefeller University Press

Moriah J. Castleman, Raul M. Torres and colleagues (University of Colorado Anschutz Medical Campus) show that BND cells demonstrate phenotypical and functional changes indicative of a loss of anergy with severe SARS-CoV-2 infection, and these changes correlate with increased systemic inflammation and autoreactive antibodies. Together, this data suggests that viral infection relaxes peripheral B cell tolerance.

BND cells demonstrate phenotypical and functional changes indicative of a loss of anergy with severe SARS-CoV-2 infection, and these changes correlate with incr

Joseph Kelich, Emmanuel Skordalakes (The Wistar Institute), Coline H.M. van Moorsel and colleagues report the first know...
04/14/2022
Telomere dysfunction implicates POT1 in patients with idiopathic pulmonary fibrosis | Journal of Experimental Medicine | Rockefeller University Press

Joseph Kelich, Emmanuel Skordalakes (The Wistar Institute), Coline H.M. van Moorsel and colleagues report the first known family with pulmonary fibrosis carrying a heterozygous POT1 mutation. The family displays short telomeres, short telomere phenotypes, and genetic anticipation. The data suggest POT1(L259S) is a pathogenic driver of IPF and provide insights into gene therapy options.

This study reports the first known family with pulmonary fibrosis carrying a heterozygous POT1 mutation. The family displays short telomeres, short telomere phe

Gabrielle Rizzuto and Adrian Erlebacher (UCSF) review our current understanding of adaptive immune responses to the feto...
04/13/2022
Trophoblast antigens, fetal blood cell antigens, and the paradox of fetomaternal tolerance | Journal of Experimental Medicine | Rockefeller University Press

Gabrielle Rizzuto and Adrian Erlebacher (UCSF) review our current understanding of adaptive immune responses to the fetoplacental allograft, emphasizing the divergent responses observed for trophoblast- versus fetal blood cell–derived antigens. We suggest these divergent responses arise from cell type–specific glycosylation programs that impart trophoblast-derived antigens with immunosuppressive properties.

We review our current understanding of adaptive immune responses to the fetoplacental allograft, emphasizing the divergent responses observed for trophoblast- v

In this review, Samarth Durgam, Maria-Luisa Alegre & Anita Chong (The University of Chicago) discuss the divergent immun...
04/13/2022
Toward an understanding of allogeneic conflict in pregnancy and transplantation | Journal of Experimental Medicine | Rockefeller University Press

In this review, Samarth Durgam, Maria-Luisa Alegre & Anita Chong (The University of Chicago) discuss the divergent immunological effects of pregnancy on T cell and humoral immunity, how prior pregnancy impacts responses upon alloantigen re-encounter in the context of solid organ transplantation, and potential strategies for controlling pregnancy-dependent allosensitization.

Discussion on the divergent immunological effects of pregnancy on T cell and humoral immunity, how prior pregnancy impacts responses upon alloantigen re-encount

In a new Insights article, Jakub Bunk and Lawrence Kazak (McGill University) highlight work by Yin and colleagues (https...
04/12/2022
Calcium burns beige | Journal of Experimental Medicine | Rockefeller University Press

In a new Insights article, Jakub Bunk and Lawrence Kazak (McGill University) highlight work by Yin and colleagues (https://bit.ly/3KAdy0p) that discovered that loss of FNIP1 is associated with browning of white adipose tissue, which they propose is driven by decreased calcium uptake into the ER.

In this issue of Journal of Experimental Medicine, Yin et al. (2022) discover that loss of FNIP1 is associated with browning of white adipose tissue, which they

Metabolically beneficial beige adipocytes offer tremendous potential to treat obesity and metabolic diseases. Yujing Yin...
04/12/2022
FNIP1 regulates adipocyte browning and systemic glucose homeostasis in mice by shaping intracellular calcium dynamics

Metabolically beneficial beige adipocytes offer tremendous potential to treat obesity and metabolic diseases. Yujing Yin, Dengqiu Xu, Yan Mao, Zhenji Gan and colleagues (Nanjing University) show that FNIP1 acts as a negative regulator of beige adipocyte thermogenesis to control systemic glucose homeostasis by modulating the ER Ca2+-ATPase SERCA.

Metabolically beneficial beige adipocytes offer tremendous potential to treat obesity and metabolic diseases. Yin et al. show that FNIP1 acts as a negative regu

This preclinical study from Jianxin Wang, May Tun Saung, Lei Zheng et al. (Johns Hopkins Kimmel Cancer Center) showed th...
04/11/2022
CCR2/CCR5 inhibitor permits the radiation-induced effector T cell infiltration in pancreatic adenocarcinoma | Journal of Experimental Medicine | Rockefeller University Press

This preclinical study from Jianxin Wang, May Tun Saung, Lei Zheng et al. (Johns Hopkins Kimmel Cancer Center) showed that CCR2/CCR5 dual-antagonist counteracts radiation-induced suppressive signals in myeloid cells and upregulates the effector T cell pathway and supported the ongoing clinical trial of the combination therapy of radiation, CCR2/CCR5 dual-antagonist, and anti–PD-1 antibody for locally advanced pancreatic cancer.

This preclinical study showed that CCR2/CCR5 dual-antagonist counteracts radiation-induced suppressive signals in myeloid cells and upregulates the effector T c

Changes in monocyte state occur during inflammation. Mysore, Tahir, Furuhashi, Mayadas and colleagues (Brigham and Women...
04/11/2022
Monocytes transition to macrophages within the inflamed vasculature via monocyte CCR2 and endothelial TNFR2

Changes in monocyte state occur during inflammation. Mysore, Tahir, Furuhashi, Mayadas and colleagues (Brigham and Women's Hospital) show that following glomerular inflammation, CCR2+CX3CR1+ double-positive monocytes, which are preferentially recruited, acquire macrophage features while still within the renal vasculature, in a process requiring CCR2 on monocytes and TNF-TNFR2–activated endothelial cells.

Changes in monocyte state occur during inflammation. We show that following glomerular inflammation, CCR2+CX3CR1+ double-positive monocytes, which are preferent

Xing Chen, Junjie Zhao, Tomasz Herjan, Lingzi Hong, Xiao Li, Xiaoxia Li and colleagues (Cleveland Clinic Lerner Research...
04/07/2022
IL-17–induced HIF1α drives resistance to anti–PD-L1 via fibroblast-mediated immune exclusion

Xing Chen, Junjie Zhao, Tomasz Herjan, Lingzi Hong, Xiao Li, Xiaoxia Li and colleagues (Cleveland Clinic Lerner Research Institute) uncover a novel mechanism whereby IL-17 signaling drives immune exclusion by activating a HIF1α-mediated collagen deposition program in cancer-associated fibroblasts in murine skin tumor models.

This study uncovers a novel mechanism whereby IL-17 signaling drives immune exclusion by activating a HIF1α-mediated collagen deposition program in cancer-assoc

We're pleased to present a special collection to accompany American Association for Cancer Research (AACR) Annual Meetin...
04/07/2022
JEM Cancer Collection 2022 | Journal of Experimental Medicine | Rockefeller University Press

We're pleased to present a special collection to accompany American Association for Cancer Research (AACR) Annual Meeting #AACR22. The collection reflects the advent of new lines of cancer research, including studies on the tumor microenvironment, tumor metabolism, anti-tumor immunity, and innovative anti-cancer therapies. We hope you appreciate this collection and encourage your comments!

Journal of Experimental Medicine (JEM) has long been a home to outstanding studies on cancer-related topics. This special collection of JEM papers reflects the advent of new lines of cancer research, including studies on the tumor microenvironment, tumo...

Alexander O. Mann, Bola S. Hanna, Diane Mathis (Harvard Medical School) and colleagues report the accrual of a populatio...
04/05/2022
IL-17A–producing γδT cells promote muscle regeneration in a microbiota-dependent manner

Alexander O. Mann, Bola S. Hanna, Diane Mathis (Harvard Medical School) and colleagues report the accrual of a population of IL-17–producing γδT cells shortly after acute injury of murine skeletal muscle. This microbiota-dependent population promotes muscle repair in an IL-17A– and neutrophil-dependent manner.

Mann et al. report the accrual of a population of IL-17–producing γδT cells shortly after acute injury of murine skeletal muscle. This microbiota-dependent popu

We are pleased to present a special collection of articles to accompany this week's virtual annual meeting of the Henry ...
04/05/2022
Innate Immunity: From Basic Biology to Human Disease | Journal of Experimental Medicine | Rockefeller University Press

We are pleased to present a special collection of articles to accompany this week's virtual annual meeting of the Henry Kunkel Society. The meeting, which is on the theme of Innate Immunity: From Basic Biology to Human Disease, will take place online April 7–9, and can be attended free of charge: https://bit.ly/2KC8kmO

Read the collection 👉

We are pleased to present a special collection of articles recently published in JEM highlighting the latest discoveries related to innate immunity, from basic biology to human pathologies. We hope you will appreciate this collection, which includes a w...

A new preclinical study has shown that once-weekly prednisone has very different results, promoting nutrient uptake into...
04/04/2022
Could Weekly, Not Daily Prednisone Represent A New Approach to Obesity Therapy?

A new preclinical study has shown that once-weekly prednisone has very different results, promoting nutrient uptake into muscles and improving lean body mass. Genetic Engineering & Biotechnology News highlights JEM study from Quattrocelli et al. (https://bit.ly/3uM5xyL):

A new study in high fat diet-fed mice showed that weekly prednisone promotes nutrient uptake into muscles, and improves lean body mass and exercise tolerance.

Our April cover shows immunohistochemistry of the first molar at P12. Periodontal tip–like endothelial cells (POTCs) per...
04/04/2022

Our April cover shows immunohistochemistry of the first molar at P12. Periodontal tip–like endothelial cells (POTCs) perforate the basal layer of odontoblasts marked by Osterix (green). Nestin (red) demarcates apical processes consisting of intermediate filament protein, while Emcn (white) labels vessel populations. Blue staining corresponds to nuclei (DAPI). Tomoko Matsubara et al. show that coupling of angiogenesis and odontogenesis orchestrates tooth mineralization in mice. https://bit.ly/3558Bx3
Read JEM's April issue: https://bit.ly/3JSDeF0

Carlos Perez-Sanchez, Ariana Barbera Betancourt, Paul A. Lyons, Kenneth G.C. Smith (University of Cambridge) and colleag...
04/01/2022
miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease | Journal of Experimental Medicine | Rockefeller University Press

Carlos Perez-Sanchez, Ariana Barbera Betancourt, Paul A. Lyons, Kenneth G.C. Smith (University of Cambridge) and colleagues suggest that miR-374a-5p is a central regulator in IBD, as its down-regulation increases the expression of a module of key inflammatory mediators. miR-374a-5p up-regulation in vitro ameliorated the increased monocyte-driven inflammation by reducing proinflammatory mediators, migration capacity, and T cell activation. miR-374a-5p has a therapeutic potential in immune-mediated diseases.

miR-374a-5p is a central regulator in IBD, as its down-regulation increases the expression of a module of key inflammatory mediators. miR-374a-5p up-regulation

Mattia Quattrocelli et al. (Cincinnati Children's Hospital Medical Center) report that chronic daily intake of exogenous...
04/01/2022
Intermittent prednisone treatment in mice promotes exercise tolerance in obesity through adiponectin

Mattia Quattrocelli et al. (Cincinnati Children's Hospital Medical Center) report that chronic daily intake of exogenous glucocorticoids produces or exacerbates metabolic stress. In contrast, this study reports that intermittent, once-weekly dosing of the glucocorticoid prednisone promotes exercise tolerance and muscle metabolism in mice with diet-induced obesity through adiponectin elevation.

Chronic daily intake of exogenous glucocorticoids produces or exacerbates metabolic stress. In contrast, this study reports that intermittent, once-weekly dosin

Madeline Churchill, Amanda W. Lund (NYU Langone Health) and colleagues demonstrate that cutaneous vaccinia virus infecti...
03/30/2022
Infection-induced lymphatic zippering restricts fluid transport and viral dissemination from skin

Madeline Churchill, Amanda W. Lund (NYU Langone Health) and colleagues demonstrate that cutaneous vaccinia virus infection induces VEGFR2-dependent dermal lymphatic capillary zippering and lymph node lymphangiogenesis, which exacerbates tissue edema, sequesters virus, and promotes CD8+ T cell responses. The lymphatic network is therefore an active barrier that contributes to innate host defense.

Cutaneous vaccinia virus infection induces VEGFR2-dependent dermal lymphatic capillary zippering and lymph node lymphangiogenesis, which exacerbates tissue edem

Yawen Chen, Xianwei Wang, Zhigang Tian et al. (University of Science and Technology of China) uncover the transcriptiona...
03/29/2022
Ly49E separates liver ILC1s into embryo-derived and postnatal subsets with different functions

Yawen Chen, Xianwei Wang, Zhigang Tian et al. (University of Science and Technology of China) uncover the transcriptional, developmental, and functional heterogeneity of ILC1s and demonstrate the dynamic changes that occur in ILC1 subsets from different origins during ontogeny, which correspond to their different functional roles, facilitating adaptation to age-related immune demands.

Chen et al. uncovered the transcriptional, developmental, and functional heterogeneity of ILC1s and demonstrated the dynamic changes that occur in ILC1 subsets

Huihui Zhang, Lei Sun, Feng Qian and colleagues (Shanghai Jiao Tong University) demonstrate that the E3 ubiquitin ligase...
03/25/2022
AMFR drives allergic asthma development by promoting alveolar macrophage–derived GM-CSF production

Huihui Zhang, Lei Sun, Feng Qian and colleagues (Shanghai Jiao Tong University) demonstrate that the E3 ubiquitin ligase autocrine motility factor receptor (AMFR) drives lung inflammation in asthma through promoting alveolar macrophage–derived GM-CSF production, and may emerge as a new potential drug target for asthma therapy.

This study demonstrates that E3 ubiquitin ligase autocrine motility factor receptor (AMFR) drives lung inflammation in asthma through promoting alveolar macroph

In the early, limited time frame of neuropathic pain, mGluR5 reemerges in cortical astrocytes, causing drastic increases...
03/25/2022
Transient astrocytic mGluR5 expression drives synaptic plasticity and subsequent chronic pain in mice | Journal of Experimental Medicine | Rockefeller University Press

In the early, limited time frame of neuropathic pain, mGluR5 reemerges in cortical astrocytes, causing drastic increases in synapse and network remodeling, leading to intractable mechanical allodynia. Despite its restricted expression, astrocytic mGluR5 plays a determinant role in subsequent brain functions.
A new study from Yosuke Danjo, Schuichi Koizumi (University of Yamanashi 山梨大学) and colleagues

In the early, limited time frame of neuropathic pain, mGluR5 reemerges in cortical astrocytes, causing drastic increases in synapse and network remodeling, lead

CD16 is a potent activating receptor in human NK cells but is weakly responsive in mouse NK cells. Oscar A. Aguilar, Lew...
03/24/2022
CD3ζ adaptor structure determines functional differences between human and mouse CD16 Fc receptor signaling

CD16 is a potent activating receptor in human NK cells but is weakly responsive in mouse NK cells. Oscar A. Aguilar, Lewis L. Lanier and colleagues (UCSF) demonstrate that this is due to differences in amino acids in the transmembrane of CD3ζ that facilitate receptor assembly and function.

CD16 is a potent activating receptor in human NK cells but is weakly responsive in mouse NK cells. Aguilar et al. demonstrate that this is due to differences in

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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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X. Tao, R. Zhang, R. Du, T. Yu, Y. Shen (Tianjin Medical University) and colleagues show that activation of E-prostanoid 3 receptor (EP3) ameliorates injury-induced liver fibrosis through promoting NK cell adhesion and killing of activated hepatic stellate cells in mice, indicating that EP3 may serve as a potential therapeutic target for liver fibrosis.
Moriah J. Castleman, Raul M. Torres and colleagues (University of Colorado Anschutz Medical Campus) show that BND cells demonstrate phenotypical and functional changes indicative of a loss of anergy with severe SARS-CoV-2 infection, and these changes correlate with increased systemic inflammation and autoreactive antibodies. Together, this data suggests that viral infection relaxes peripheral B cell tolerance.
Joseph Kelich, Emmanuel Skordalakes (The Wistar Institute), Coline H.M. van Moorsel and colleagues report the first known family with pulmonary fibrosis carrying a heterozygous POT1 mutation. The family displays short telomeres, short telomere phenotypes, and genetic anticipation. The data suggest POT1(L259S) is a pathogenic driver of IPF and provide insights into gene therapy options.
Gabrielle Rizzuto and Adrian Erlebacher (UCSF) review our current understanding of adaptive immune responses to the fetoplacental allograft, emphasizing the divergent responses observed for trophoblast- versus fetal blood cell–derived antigens. We suggest these divergent responses arise from cell type–specific glycosylation programs that impart trophoblast-derived antigens with immunosuppressive properties.
In this review, Samarth Durgam, Maria-Luisa Alegre & Anita Chong (The University of Chicago) discuss the divergent immunological effects of pregnancy on T cell and humoral immunity, how prior pregnancy impacts responses upon alloantigen re-encounter in the context of solid organ transplantation, and potential strategies for controlling pregnancy-dependent allosensitization.
In a new Insights article, Jakub Bunk and Lawrence Kazak (McGill University) highlight work by Yin and colleagues (https://bit.ly/3KAdy0p) that discovered that loss of FNIP1 is associated with browning of white adipose tissue, which they propose is driven by decreased calcium uptake into the ER.
Metabolically beneficial beige adipocytes offer tremendous potential to treat obesity and metabolic diseases. Yujing Yin, Dengqiu Xu, Yan Mao, Zhenji Gan and colleagues (Nanjing University) show that FNIP1 acts as a negative regulator of beige adipocyte thermogenesis to control systemic glucose homeostasis by modulating the ER Ca2+-ATPase SERCA.
This preclinical study from Jianxin Wang, May Tun Saung, Lei Zheng et al. (Johns Hopkins Kimmel Cancer Center) showed that CCR2/CCR5 dual-antagonist counteracts radiation-induced suppressive signals in myeloid cells and upregulates the effector T cell pathway and supported the ongoing clinical trial of the combination therapy of radiation, CCR2/CCR5 dual-antagonist, and anti–PD-1 antibody for locally advanced pancreatic cancer.
Changes in monocyte state occur during inflammation. Mysore, Tahir, Furuhashi, Mayadas and colleagues (Brigham and Women's Hospital) show that following glomerular inflammation, CCR2+CX3CR1+ double-positive monocytes, which are preferentially recruited, acquire macrophage features while still within the renal vasculature, in a process requiring CCR2 on monocytes and TNF-TNFR2–activated endothelial cells.
Xing Chen, Junjie Zhao, Tomasz Herjan, Lingzi Hong, Xiao Li, Xiaoxia Li and colleagues (Cleveland Clinic Lerner Research Institute) uncover a novel mechanism whereby IL-17 signaling drives immune exclusion by activating a HIF1α-mediated collagen deposition program in cancer-associated fibroblasts in murine skin tumor models.
We're pleased to present a special collection to accompany American Association for Cancer Research (AACR) Annual Meeting #AACR22. The collection reflects the advent of new lines of cancer research, including studies on the tumor microenvironment, tumor metabolism, anti-tumor immunity, and innovative anti-cancer therapies. We hope you appreciate this collection and encourage your comments!
Alexander O. Mann, Bola S. Hanna, Diane Mathis (Harvard Medical School) and colleagues report the accrual of a population of IL-17–producing γδT cells shortly after acute injury of murine skeletal muscle. This microbiota-dependent population promotes muscle repair in an IL-17A– and neutrophil-dependent manner.