journal
MENU ▼
Read by QxMD icon Read
search

Journal of Experimental Medicine

journal
https://www.readbyqxmd.com/read/29150429/cgamp-a-tale-of-two-signals
#1
Teneema Kuriakose, Thirumala-Devi Kanneganti
In this issue of JEM, Swanson et al. (https://doi.org/10.1084/jem.20171749) report an unanticipated role for cGAMP in priming and activation of inflammasomes in addition to its well-characterized function as an endogenous second messenger inducing type I interferons in the cytosolic DNA-sensing pathway.
November 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29141870/ig%C3%AE-ubiquitination-activates-pi3k-signals-required-for-endosomal-sorting
#2
Margaret Veselits, Azusa Tanaka, Yaoqing Chen, Keith Hamel, Malay Mandal, Matheswaran Kandasamy, Balaji Manicassamy, Shannon K O'Neill, Patrick Wilson, Roger Sciammas, Marcus R Clark
A wealth of in vitro data has demonstrated a central role for receptor ubiquitination in endocytic sorting. However, how receptor ubiquitination functions in vivo is poorly understood. Herein, we report that ablation of B cell antigen receptor ubiquitination in vivo uncouples the receptor from CD19 phosphorylation and phosphatidylinositol 3-kinase (PI3K) signals. These signals are necessary and sufficient for accumulating phosphatidylinositol (3,4,5)-trisphosphate (PIP3) on B cell receptor-containing early endosomes and proper sorting into the MHC class II antigen-presenting compartment (MIIC)...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29141869/human-stem-cell-derived-astrocytes-replicate-human-prions-in-a-prnp-genotype-dependent-manner
#3
Zuzana Krejciova, James Alibhai, Chen Zhao, Robert Krencik, Nina M Rzechorzek, Erik M Ullian, Jean Manson, James W Ironside, Mark W Head, Siddharthan Chandran
Prions are infectious agents that cause neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD). The absence of a human cell culture model that replicates human prions has hampered prion disease research for decades. In this paper, we show that astrocytes derived from human induced pluripotent stem cells (iPSCs) support the replication of prions from brain samples of CJD patients. For experimental exposure of astrocytes to variant CJD (vCJD), the kinetics of prion replication occur in a prion protein codon 129 genotype-dependent manner, reflecting the genotype-dependent susceptibility to clinical vCJD found in patients...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29141868/geographic-clonal-tracking-in-macaques-provides-insights-into-hspc-migration-and-differentiation
#4
Chuanfeng Wu, Diego A Espinoza, Samson J Koelle, E Lake Potter, Rong Lu, Brian Li, Di Yang, Xing Fan, Robert E Donahue, Mario Roederer, Cynthia E Dunbar
The geographic distribution of hematopoiesis at a clonal level is of interest in understanding how hematopoietic stem and progenitor cells (HSPCs) and their progeny interact with bone marrow (BM) niches during regeneration. We tagged rhesus macaque autologous HSPCs with genetic barcodes, allowing clonal tracking over time and space after transplantation. We found marked geographic segregation of CD34(+) HSPCs for at least 6 mo posttransplantation, followed by very gradual clonal mixing at different BM sites over subsequent months to years...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29141867/host-resistance-to-endotoxic-shock-requires-the-neuroendocrine-regulation-of-group-1-innate-lymphoid-cells
#5
Linda Quatrini, Elisabeth Wieduwild, Sophie Guia, Claire Bernat, Nicolas Glaichenhaus, Eric Vivier, Sophie Ugolini
Upon infection, the immune system produces inflammatory mediators important for pathogen clearance. However, inflammation can also have deleterious effect on the host and is tightly regulated. Immune system-derived cytokines stimulate the hypothalamic-pituitary-adrenal (HPA) axis, triggering endogenous glucocorticoid production. Through interaction with ubiquitously expressed glucocorticoid receptors (GRs), this steroid hormone has pleiotropic effects on many cell types. Using a genetic mouse model in which the gene encoding the GR is selectively deleted in NKp46(+) innate lymphoid cells (ILCs), we demonstrated a major role for the HPA pathway in host resistance to endotoxin-induced septic shock...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29141866/prostate-specific-membrane-antigen-cleavage-of-vitamin-b9-stimulates-oncogenic-signaling-through-metabotropic-glutamate-receptors
#6
Charalambos Kaittanis, Chrysafis Andreou, Haley Hieronymus, Ninghui Mao, Catherine A Foss, Matthias Eiber, Gregor Weirich, Palak Panchal, Anuradha Gopalan, Juan Zurita, Samuel Achilefu, Gabriela Chiosis, Vladimir Ponomarev, Markus Schwaiger, Brett S Carver, Martin G Pomper, Jan Grimm
Prostate-specific membrane antigen (PSMA) or folate hydrolase 1 (FOLH1) is highly expressed on prostate cancer. Its expression correlates inversely with survival and increases with tumor grade. However, the biological role of PSMA has not been explored, and its role in prostate cancer remained elusive. Filling this gap, we demonstrate that in prostate cancer, PSMA initiates signaling upstream of PI3K through G protein-coupled receptors, specifically via the metabotropic glutamate receptor (mGluR). PSMA's carboxypeptidase activity releases glutamate from vitamin B9 and other glutamated substrates, which activate mGluR I...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29141865/development-and-plasticity-of-meningeal-lymphatic-vessels
#7
Salli Antila, Sinem Karaman, Harri Nurmi, Mikko Airavaara, Merja H Voutilainen, Thomas Mathivet, Dmitri Chilov, Zhilin Li, Tapani Koppinen, Jun-Hee Park, Shentong Fang, Aleksanteri Aspelund, Mart Saarma, Anne Eichmann, Jean-Léon Thomas, Kari Alitalo
The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement in neuropathological processes, yet little is known about their development or maintenance. We show here that meningeal LVs develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system (CNS). VEGF-C, expressed mainly in vascular smooth muscle cells, and VEGFR3 in lymphatic endothelial cells were essential for their development, whereas VEGF-D deletion had no effect...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29138248/usp1-uaf1-deubiquitinase-complex-stabilizes-tbk1-and-enhances-antiviral-responses
#8
Zhongxia Yu, Hui Song, Mutian Jia, Jintao Zhang, Wenwen Wang, Qi Li, Lining Zhang, Wei Zhao
Optimal activation of TANK-binding kinase 1 (TBK1) is crucial for initiation of innate antiviral immunity and maintenance of immune homeostasis. Although several E3 ubiquitin ligases have been reported to regulate TBK1 activation by mediating its polyubiquitination, the functions of deubiquitinase on TBK1 activity remain largely unclear. Here, we identified a deubiquitinase complex, which is formed by ubiquitin specific peptidase 1 (USP1) and USP1-associated factor 1 (UAF1), as a viral infection-induced physiological enhancer of TBK1 expression...
November 14, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29127204/mutations-in-the-x-linked-atp6ap2-cause-a-glycosylation-disorder-with-autophagic-defects
#9
Maria A Rujano, Magda Cannata Serio, Ganna Panasyuk, Romain Péanne, Janine Reunert, Daisy Rymen, Virginie Hauser, Julien H Park, Peter Freisinger, Erika Souche, Maria Clara Guida, Esther M Maier, Yoshinao Wada, Stefanie Jäger, Nevan J Krogan, Oliver Kretz, Susana Nobre, Paula Garcia, Dulce Quelhas, Thomas D Bird, Wendy H Raskind, Michael Schwake, Sandrine Duvet, Francois Foulquier, Gert Matthijs, Thorsten Marquardt, Matias Simons
The biogenesis of the multi-subunit vacuolar-type H(+)-ATPase (V-ATPase) is initiated in the endoplasmic reticulum with the assembly of the proton pore V0, which is controlled by a group of assembly factors. Here, we identify two hemizygous missense mutations in the extracellular domain of the accessory V-ATPase subunit ATP6AP2 (also known as the [pro]renin receptor) responsible for a glycosylation disorder with liver disease, immunodeficiency, cutis laxa, and psychomotor impairment. We show that ATP6AP2 deficiency in the mouse liver caused hypoglycosylation of serum proteins and autophagy defects...
November 10, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29122948/microrna-regulation-of-type-2-innate-lymphoid-cell-homeostasis-and-function-in-allergic-inflammation
#10
Priti B Singh, Heather H Pua, Hannah C Happ, Christoph Schneider, Jakob von Moltke, Richard M Locksley, Dirk Baumjohann, K Mark Ansel
MicroRNAs (miRNAs) exert powerful effects on immunity through coordinate regulation of multiple target genes in a wide variety of cells. Type 2 innate lymphoid cells (ILC2s) are tissue sentinel mediators of allergic inflammation. We established the physiological requirements for miRNAs in ILC2 homeostasis and immune function and compared the global miRNA repertoire of resting and activated ILC2s and T helper type 2 (TH2) cells. After exposure to the natural allergen papain, mice selectively lacking the miR-17∼92 cluster in ILC2s displayed reduced lung inflammation...
November 9, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29122947/phosphorylation-promotes-activation-induced-cytidine-deaminase-activity-at-the-myc-oncogene
#11
Yunxiang Mu, Monika A Zelazowska, Kevin M McBride
Activation-induced cytidine deaminase (AID) is a mutator enzyme that targets immunoglobulin (Ig) genes to initiate antibody somatic hypermutation (SHM) and class switch recombination (CSR). Off-target AID association also occurs, which causes oncogenic mutations and chromosome rearrangements. However, AID occupancy does not directly correlate with DNA damage, suggesting that factors beyond AID association contribute to mutation targeting. CSR and SHM are regulated by phosphorylation on AID serine38 (pS38), but the role of pS38 in off-target activity has not been evaluated...
November 9, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29114065/bim-suppresses-the-development-of-sle-by-limiting-myeloid-inflammatory-responses
#12
FuNien Tsai, Philip J Homan, Hemant Agrawal, Alexander V Misharin, Hiam Abdala-Valencia, G Kenneth Haines, Salina Dominguez, Christina L Bloomfield, Rana Saber, Anthony Chang, Chandra Mohan, Jack Hutcheson, Anne Davidson, G R Scott Budinger, Philippe Bouillet, Andrea Dorfleutner, Christian Stehlik, Deborah R Winter, Carla M Cuda, Harris Perlman
The Bcl-2 family is considered the guardian of the mitochondrial apoptotic pathway. We demonstrate that Bim acts as a molecular rheostat by controlling macrophage function not only in lymphoid organs but also in end organs, thereby preventing the break in tolerance. Mice lacking Bim in myeloid cells (LysM(Cre)Bim(fl/fl)) develop a systemic lupus erythematosus (SLE)-like disease that mirrors aged Bim(-/-) mice, including loss of marginal zone macrophages, splenomegaly, lymphadenopathy, autoantibodies (including anti-DNA IgG), and a type I interferon signature...
November 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29114064/sorla-attenuates-epha4-signaling-and-amyloid-%C3%AE-induced-neurodegeneration
#13
Timothy Y Huang, Yingjun Zhao, Lu-Lin Jiang, Xiaoguang Li, Yan Liu, Yu Sun, Juan C Piña-Crespo, Bing Zhu, Eliezer Masliah, Thomas E Willnow, Elena B Pasquale, Huaxi Xu
Sortilin-related receptor with LDLR class A repeats (SORLA, SORL1, or LR11) is a genetic risk factor associated with Alzheimer's disease (AD). Although SORLA is known to regulate trafficking of the amyloid β (Aβ) precursor protein to decrease levels of proteotoxic Aβ oligomers, whether SORLA can counteract synaptic dysfunction induced by Aβ oligomers remains unclear. Here, we show that SORLA interacts with the EphA4 receptor tyrosine kinase and attenuates ephrinA1 ligand-induced EphA4 clustering and activation to limit downstream effects of EphA4 signaling in neurons...
November 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29101251/the-methyltransferase-nsd3-promotes-antiviral-innate-immunity-via-direct-lysine-methylation-of-irf3
#14
Chunmei Wang, Qinlan Wang, Xiaoqing Xu, Bin Xie, Yong Zhao, Nan Li, Xuetao Cao
Lysine methylation is an important posttranslational modification, implicated in various biological pathological conditions. The transcription factor interferon regulatory factor 3 (IRF3) is essential for antiviral innate immunity, yet the mechanism for methylation control of IRF3 activation remains unclear. In this paper, we discovered monomethylation of IRF3 at K366 is critical for IRF3 transcription activity in antiviral innate immunity. By mass spectrometry analysis of IRF3-associated proteins, we identified nuclear receptor-binding SET domain 3 (NSD3) as the lysine methyltransferase that directly binds to the IRF3 C-terminal region through its PWWP1 domain and methylates IRF3 at K366 via its SET domain...
November 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29097442/a-p190brhogap-mutation-and-prolonged-rhob-activation-in-fatal-systemic-capillary-leak-syndrome
#15
Richard W Pierce, Jonathan Merola, John Paul Lavik, Martin S Kluger, Anita Huttner, Mustafa K Khokha, Jordan S Pober
We describe a fatal case of pediatric systemic capillary leak (Clarkson's disease) associated with a point mutation in p190BRhoGAP. Dermal microvascular endothelial cells (ECs) isolated from this patient form monolayers with similar levels and distribution of junctional proteins and transendothelial electrical resistance compared with normal human dermal microvascular ECs. However, patient-derived ECs demonstrate a greater increase in permeability and impaired recovery of barrier function in response to tumor necrosis factor (TNF) compared with normal donor EC cultures...
November 2, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29093060/a-molecular-roadmap-of-the-agm-region-reveals-bmper-as-a-novel-regulator-of-hsc-maturation
#16
Alison C McGarvey, Stanislav Rybtsov, Céline Souilhol, Sara Tamagno, Ritva Rice, David Hills, Duncan Godwin, David Rice, Simon R Tomlinson, Alexander Medvinsky
In the developing embryo, hematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region, but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA sequencing over these spatiotemporal transitions in the AGM region and supportive OP9 cell line. Screening several proteins through an ex vivo reaggregate culture system, we identify BMPER as a novel positive regulator of HSC development...
November 1, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29089374/autophagy-protein-atg16l1-prevents-necroptosis-in-the-intestinal-epithelium
#17
Yu Matsuzawa-Ishimoto, Yusuke Shono, Luis E Gomez, Vanessa M Hubbard-Lucey, Michael Cammer, Jessica Neil, M Zahidunnabi Dewan, Sophia R Lieberman, Amina Lazrak, Jill M Marinis, Allison Beal, Philip A Harris, John Bertin, Chen Liu, Yi Ding, Marcel R M van den Brink, Ken Cadwell
A variant of the autophagy gene ATG16L1 is associated with Crohn's disease, an inflammatory bowel disease (IBD), and poor survival in allogeneic hematopoietic stem cell transplant recipients. We demonstrate that ATG16L1 in the intestinal epithelium is essential for preventing loss of Paneth cells and exaggerated cell death in animal models of virally triggered IBD and allogeneic hematopoietic stem cell transplantation. Intestinal organoids lacking ATG16L1 reproduced this loss in Paneth cells and displayed TNFα-mediated necroptosis, a form of programmed necrosis...
October 31, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29084819/mast-cells-acquire-mhcii-from-dendritic-cells-during-skin-inflammation
#18
Jan Dudeck, Anna Medyukhina, Julia Fröbel, Carl-Magnus Svensson, Johanna Kotrba, Michael Gerlach, Ann-Christine Gradtke, Bernd Schröder, Stephan Speier, Marc Thilo Figge, Anne Dudeck
Mast cells (MCs) and dendritic cells (DCs) are essential innate sentinels populating host-environment interfaces. Using longitudinal intravital multiphoton microscopy of DC(GFP)/MC(RFP) reporter mice, we herein provide in vivo evidence that migratory DCs execute targeted cell-to-cell interactions with stationary MCs before leaving the inflamed skin to draining lymph nodes. During initial stages of skin inflammation, DCs dynamically scan MCs, whereas at a later stage, long-lasting interactions predominate. These innate-to-innate synapse-like contacts ultimately culminate in DC-to-MC molecule transfers including major histocompatibility complex class II (MHCII) proteins enabling subsequent ex vivo priming of allogeneic T cells with a specific cytokine signature...
October 30, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29066578/r-spondin1-expands-paneth-cells-and-prevents-dysbiosis-induced-by-graft-versus-host-disease
#19
Eiko Hayase, Daigo Hashimoto, Kiminori Nakamura, Clara Noizat, Reiki Ogasawara, Shuichiro Takahashi, Hiroyuki Ohigashi, Yuki Yokoi, Rina Sugimoto, Satomi Matsuoka, Takahide Ara, Emi Yokoyama, Tomohiro Yamakawa, Ko Ebata, Takeshi Kondo, Rina Hiramine, Tomoyasu Aizawa, Yoshitoshi Ogura, Tetsuya Hayashi, Hiroshi Mori, Ken Kurokawa, Kazuma Tomizuka, Tokiyoshi Ayabe, Takanori Teshima
The intestinal microbial ecosystem is actively regulated by Paneth cell-derived antimicrobial peptides such as α-defensins. Various disorders, including graft-versus-host disease (GVHD), disrupt Paneth cell functions, resulting in unfavorably altered intestinal microbiota (dysbiosis), which further accelerates the underlying diseases. Current strategies to restore the gut ecosystem are bacteriotherapy such as fecal microbiota transplantation and probiotics, and no physiological approach has been developed so far...
October 24, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29066577/identification-and-characterization-of-t-reg-like-cells-in-zebrafish
#20
Melissa Kasheta, Corrie A Painter, Finola E Moore, Riadh Lobbardi, Alysia Bryll, Eli Freiman, David Stachura, Arlin B Rogers, Yariv Houvras, David M Langenau, Craig J Ceol
Regulatory T (T reg) cells are a specialized sublineage of T lymphocytes that suppress autoreactive T cells. Functional studies of T reg cells in vitro have defined multiple suppression mechanisms, and studies of T reg-deficient humans and mice have made clear the important role that these cells play in preventing autoimmunity. However, many questions remain about how T reg cells act in vivo. Specifically, it is not clear which suppression mechanisms are most important, where T reg cells act, and how they get there...
October 24, 2017: Journal of Experimental Medicine
journal
journal
25530
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"