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Nature Immunology

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https://www.readbyqxmd.com/read/28092375/postprandial-macrophage-derived-il-1%C3%AE-stimulates-insulin-and-both-synergistically-promote-glucose-disposal-and-inflammation
#1
Erez Dror, Elise Dalmas, Daniel T Meier, Stephan Wueest, Julien Thévenet, Constanze Thienel, Katharina Timper, Thierry M Nordmann, Shuyang Traub, Friederike Schulze, Flurin Item, David Vallois, Francois Pattou, Julie Kerr-Conte, Vanessa Lavallard, Thierry Berney, Bernard Thorens, Daniel Konrad, Marianne Böni-Schnetzler, Marc Y Donath
The deleterious effect of chronic activation of the IL-1β system on type 2 diabetes and other metabolic diseases is well documented. However, a possible physiological role for IL-1β in glucose metabolism has remained unexplored. Here we found that feeding induced a physiological increase in the number of peritoneal macrophages that secreted IL-1β, in a glucose-dependent manner. Subsequently, IL-1β contributed to the postprandial stimulation of insulin secretion. Accordingly, lack of endogenous IL-1β signaling in mice during refeeding and obesity diminished the concentration of insulin in plasma...
January 16, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28092373/chronic-signaling-via-the-metabolic-checkpoint-kinase-mtorc1-induces-macrophage-granuloma-formation-and-marks-sarcoidosis-progression
#2
Monika Linke, Ha Thi Thanh Pham, Karl Katholnig, Thomas Schnöller, Anne Miller, Florian Demel, Birgit Schütz, Margit Rosner, Boris Kovacic, Nyamdelger Sukhbaatar, Birgit Niederreiter, Stephan Blüml, Peter Kuess, Veronika Sexl, Mathias Müller, Mario Mikula, Wolfram Weckwerth, Arvand Haschemi, Martin Susani, Markus Hengstschläger, Michael J Gambello, Thomas Weichhart
The aggregation of hypertrophic macrophages constitutes the basis of all granulomatous diseases, such as tuberculosis or sarcoidosis, and is decisive for disease pathogenesis. However, macrophage-intrinsic pathways driving granuloma initiation and maintenance remain elusive. We found that activation of the metabolic checkpoint kinase mTORC1 in macrophages by deletion of the gene encoding tuberous sclerosis 2 (Tsc2) was sufficient to induce hypertrophy and proliferation, resulting in excessive granuloma formation in vivo...
January 16, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28092372/direct-control-of-regulatory-t-cells-by-keratinocytes
#3
Mariko Kashiwagi, Junichi Hosoi, Jen-Feng Lai, Janice Brissette, Steven F Ziegler, Bruce A Morgan, Katia Georgopoulos
Environmental challenges to epithelial cells trigger gene expression changes that elicit context-appropriate immune responses. We found that the chromatin remodeler Mi-2β controls epidermal homeostasis by regulating the genes involved in keratinocyte and immune-cell activation to maintain an inactive state. Mi-2β depletion resulted in rapid deployment of both a pro-inflammatory and an immunosuppressive response in the skin. A key target of Mi-2β in keratinocytes is the pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP)...
January 16, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28068307/transitional-b-cells-commit-to-marginal-zone-b-cell-fate-by-taok3-mediated-surface-expression-of-adam10
#4
Hamida Hammad, Matthias Vanderkerken, Philippe Pouliot, Kim Deswarte, Wendy Toussaint, Karl Vergote, Lana Vandersarren, Sophie Janssens, Ioanna Ramou, Savvas N Savvides, Jody J Haigh, Rudi Hendriks, Manfred Kopf, Katleen Craessaerts, Bart de Strooper, John F Kearney, Daniel H Conrad, Bart N Lambrecht
Notch2 and B cell antigen receptor (BCR) signaling determine whether transitional B cells become marginal zone B (MZB) or follicular B (FoB) cells in the spleen, but it is unknown how these pathways are related. We generated Taok3(-/-) mice, lacking the serine/threonine kinase Taok3, and found cell-intrinsic defects in the development of MZB but not FoB cells. Type 1 transitional (T1) B cells required Taok3 to rapidly respond to ligation by the Notch ligand Delta-like 1. BCR ligation by endogenous or exogenous ligands induced the surface expression of the metalloproteinase ADAM10 on T1 B cells in a Taok3-dependent manner...
January 9, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28092377/neuroimmune-communication
#5
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/28092376/infectious-immunity-in-the-central-nervous-system-and-brain-function
#6
REVIEW
Robyn S Klein, Charise Garber, Nicole Howard
Inflammation is emerging as a critical mechanism underlying neurological disorders of various etiologies, yet its role in altering brain function as a consequence of neuroinfectious disease remains unclear. Although acute alterations in mental status due to inflammation are a hallmark of central nervous system (CNS) infections with neurotropic pathogens, post-infectious neurologic dysfunction has traditionally been attributed to irreversible damage caused by the pathogens themselves. More recently, studies indicate that pathogen eradication within the CNS may require immune responses that interfere with neural cell function and communication without affecting their survival...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/28092374/the-movers-and-shapers-in-immune-privilege-of-the-cns
#7
REVIEW
Britta Engelhardt, Peter Vajkoczy, Roy O Weller
Discoveries leading to an improved understanding of immune surveillance of the central nervous system (CNS) have repeatedly provoked dismissal of the existence of immune privilege of the CNS. Recent rediscoveries of lymphatic vessels within the dura mater surrounding the brain, made possible by modern live-cell imaging technologies, have revived this discussion. This review emphasizes the fact that understanding immune privilege of the CNS requires intimate knowledge of its unique anatomy. Endothelial, epithelial and glial brain barriers establish compartments in the CNS that differ strikingly with regard to their accessibility to immune-cell subsets...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/28092371/neuroimmune-regulation-during-intestinal-development-and-homeostasis
#8
REVIEW
Henrique Veiga-Fernandes, Vassilis Pachnis
Interactions between the nervous system and immune system are required for organ function and homeostasis. Evidence suggests that enteric neurons and intestinal immune cells share common regulatory mechanisms and can coordinate their responses to developmental challenges and environmental aggressions. These discoveries shed light on the physiology of system interactions and open novel perspectives for therapy designs that target underappreciated neurological-immunological commonalities. Here we highlight findings that address the importance of neuroimmune cell units (NICUs) in intestinal development, homeostasis and disease...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/28024153/hiv-1-blocks-the-signaling-adaptor-mavs-to-evade-antiviral-host-defense-after-sensing-of-abortive-hiv-1-rna-by-the-host-helicase-ddx3
#9
Sonja I Gringhuis, Nina Hertoghs, Tanja M Kaptein, Esther M Zijlstra-Willems, Ramin Sarrami-Fooroshani, Joris K Sprokholt, Nienke H van Teijlingen, Neeltje A Kootstra, Thijs Booiman, Karel A van Dort, Carla M S Ribeiro, Agata Drewniak, Teunis B H Geijtenbeek
The mechanisms by which human immunodeficiency virus 1 (HIV-1) avoids immune surveillance by dendritic cells (DCs), and thereby prevents protective adaptive immune responses, remain poorly understood. Here we showed that HIV-1 actively arrested antiviral immune responses by DCs, which contributed to efficient HIV-1 replication in infected individuals. We identified the RNA helicase DDX3 as an HIV-1 sensor that bound abortive HIV-1 RNA after HIV-1 infection and induced DC maturation and type I interferon responses via the signaling adaptor MAVS...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/28024152/ubiquitination-of-hnrnpa1-by-traf6-links-chronic-innate-immune-signaling-with-myelodysplasia
#10
Jing Fang, Lyndsey C Bolanos, Kwangmin Choi, Xiaona Liu, Susanne Christie, Shailaja Akunuru, Rupali Kumar, Dehua Wang, Xiaoting Chen, Kenneth D Greis, Peter Stoilov, Marie-Dominique Filippi, Jaroslaw P Maciejewski, Guillermo Garcia-Manero, Matthew T Weirauch, Nathan Salomonis, Hartmut Geiger, Yi Zheng, Daniel T Starczynowski
Toll-like receptor (TLR) activation contributes to premalignant hematologic conditions, such as myelodysplastic syndromes (MDS). TRAF6, a TLR effector with ubiquitin (Ub) ligase activity, is overexpressed in MDS hematopoietic stem/progenitor cells (HSPCs). We found that TRAF6 overexpression in mouse HSPC results in impaired hematopoiesis and bone marrow failure. Using a global Ub screen, we identified hnRNPA1, an RNA-binding protein and auxiliary splicing factor, as a substrate of TRAF6. TRAF6 ubiquitination of hnRNPA1 regulated alternative splicing of Arhgap1, which resulted in activation of the GTP-binding Rho family protein Cdc42 and accounted for hematopoietic defects in TRAF6-expressing HSPCs...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27992404/a-gene-network-regulated-by-the-transcription-factor-vgll3-as-a-promoter-of-sex-biased-autoimmune-diseases
#11
Yun Liang, Lam C Tsoi, Xianying Xing, Maria A Beamer, William R Swindell, Mrinal K Sarkar, Celine C Berthier, Philip E Stuart, Paul W Harms, Rajan P Nair, James T Elder, John J Voorhees, J Michelle Kahlenberg, Johann E Gudjonsson
Autoimmune diseases affect 7.5% of the US population, and they are among the leading causes of death and disability. A notable feature of many autoimmune diseases is their greater prevalence in females than in males, but the underlying mechanisms of this have remained unclear. Through the use of high-resolution global transcriptome analyses, we demonstrated a female-biased molecular signature associated with susceptibility to autoimmune disease and linked this to extensive sex-dependent co-expression networks...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27992403/themis2-lowers-the-threshold-for-b-cell-activation-during-positive-selection
#12
Daian Cheng, Mukta Deobagkar-Lele, Ekaterina Zvezdova, Seeyoung Choi, Shoji Uehara, Delphine Baup, Sophia C Bennett, Katherine R Bull, Tanya L Crockford, Helen Ferry, Claude Warzecha, Marlène Marcellin, Anne Gonzalez de Peredo, Renaud Lesourne, Consuelo Anzilotti, Paul E Love, Richard J Cornall
The positive and negative selection of lymphocytes by antigen is central to adaptive immunity and self-tolerance, yet how this is determined by different antigens is not completely understood. We found that thymocyte-selection-associated family member 2 (Themis2) increased the positive selection of B1 cells and germinal center B cells by self and foreign antigens. Themis2 lowered the threshold for B-cell activation by low-avidity, but not high-avidity, antigens. Themis2 constitutively bound the adaptor protein Grb2, src-kinase Lyn and signal transducer phospholipase γ2 (PLC-γ2), and increased activation of PLC-γ2 and its downstream pathways following B cell receptor stimulation...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27992402/the-ubiquitin-e3-ligase-trim31-promotes-aggregation-and-activation-of-the-signaling-adaptor-mavs-through-lys63-linked-polyubiquitination
#13
Bingyu Liu, Meng Zhang, Honglei Chu, Honghai Zhang, Haifeng Wu, Guanhua Song, Peng Wang, Kai Zhao, Jinxiu Hou, Xueer Wang, Lei Zhang, Chengjiang Gao
The signaling adaptor MAVS forms prion-like aggregates to activate an innate antiviral immune response after viral infection. However, the molecular mechanisms that regulate MAVS aggregation are poorly understood. Here we identified TRIM31, an E3 ubiquitin ligase of the TRIM family of proteins, as a regulator of MAVS aggregation. TRIM31 was recruited to mitochondria after viral infection and specifically regulated antiviral signaling mediated by RLR pattern-recognition receptors. TRIM31-deficient mice were more susceptible to infection with RNA virus than were wild-type mice...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27992401/guidance-of-regulatory-t-cell-development-by-satb1-dependent-super-enhancer-establishment
#14
Yohko Kitagawa, Naganari Ohkura, Yujiro Kidani, Alexis Vandenbon, Keiji Hirota, Ryoji Kawakami, Keiko Yasuda, Daisuke Motooka, Shota Nakamura, Motonari Kondo, Ichiro Taniuchi, Terumi Kohwi-Shigematsu, Shimon Sakaguchi
Most Foxp3(+) regulatory T (Treg) cells develop in the thymus as a functionally mature T cell subpopulation specialized for immune suppression. Their cell fate appears to be determined before Foxp3 expression; yet molecular events that prime Foxp3(-) Treg precursor cells are largely obscure. We found that Treg cell-specific super-enhancers (Treg-SEs), which were associated with Foxp3 and other Treg cell signature genes, began to be activated in Treg precursor cells. T cell-specific deficiency of the genome organizer Satb1 impaired Treg-SE activation and the subsequent expression of Treg signature genes, causing severe autoimmunity due to Treg cell deficiency...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27992400/the-histone-demethylase-utx-regulates-the-lineage-specific-epigenetic-program-of-invariant-natural-killer-t-cells
#15
Semir Beyaz, Ji Hyung Kim, Luca Pinello, Michael E Xifaras, Yu Hu, Jialiang Huang, Marc A Kerenyi, Partha P Das, R Anthony Barnitz, Aurelie Herault, Rizkullah Dogum, W Nicholas Haining, Ömer H Yilmaz, Emmanuelle Passegue, Guo-Cheng Yuan, Stuart H Orkin, Florian Winau
Invariant natural killer T cells (iNKT cells) are innate-like lymphocytes that protect against infection, autoimmune disease and cancer. However, little is known about the epigenetic regulation of iNKT cell development. Here we found that the H3K27me3 histone demethylase UTX was an essential cell-intrinsic factor that controlled an iNKT-cell lineage-specific gene-expression program and epigenetic landscape in a demethylase-activity-dependent manner. UTX-deficient iNKT cells exhibited impaired expression of iNKT cell signature genes due to a decrease in activation-associated H3K4me3 marks and an increase in repressive H3K27me3 marks within the promoters occupied by UTX...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27941787/recruitment-of-calcineurin-to-the-tcr-positively-regulates-t-cell-activation
#16
Debjani Dutta, Valarie A Barr, Itoro Akpan, Paul R Mittelstadt, Laishram I Singha, Lawrence E Samelson, Jonathan D Ashwell
Calcineurin is a phosphatase whose primary targets in T cells are NFAT transcription factors, and inhibition of calcineurin activity by treatment with cyclosporin A (CsA) or FK506 is a cornerstone of immunosuppressive therapies. Here we found that calcineurin was recruited to the T cell antigen receptor (TCR) signaling complex, where it reversed inhibitory phosphorylation of the tyrosine kinase Lck on Ser59 (Lck(S59)). Loss of calcineurin activity impaired phosphorylation of Tyr493 of the tyrosine kinase ZAP-70 (ZAP-70(Y493)), as well as some downstream pathways in a manner consistent with signaling in cells expressing Lck(S59A) (Lck that cannot be phosphorylated) or Lck(S59E) (a phosphomimetic mutant)...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27941786/transcriptional-programs-that-control-expression-of-the-autoimmune-regulator-gene-aire
#17
Yonatan Herzig, Shir Nevo, Chamutal Bornstein, Miriam R Brezis, Sharon Ben-Hur, Aya Shkedy, Michal Eisenberg-Bord, Ben Levi, Michael Delacher, Yael Goldfarb, Eyal David, Leehee Weinberger, Sergey Viukov, Shifra Ben-Dor, Matthieu Giraud, Jacob H Hanna, Achim Breiling, Frank Lyko, Ido Amit, Markus Feuerer, Jakub Abramson
Aire is a transcriptional regulator that induces promiscuous expression of thousands of genes encoding tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). While the target genes of Aire are well characterized, the transcriptional programs that regulate its own expression have remained elusive. Here we comprehensively analyzed both cis-acting and trans-acting regulatory mechanisms and found that the Aire locus was insulated by the global chromatin organizer CTCF and was hypermethylated in cells and tissues that did not express Aire...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/28102221/epigenetic-orchestration-of-thymic-treg-cell-development
#18
Marc Beyer, Jochen Huehn
No abstract text is available yet for this article.
January 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28102220/inkt-cells-need-utx-tra-demethylation
#19
S Harsha Krovi, Laurent Gapin
No abstract text is available yet for this article.
January 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28102219/corrigendum-the-role-of-the-local-environment-and-epigenetics-in-shaping-macrophage-identity-and-their-effect-on-tissue-homeostasis
#20
Ido Amit, Deborah R Winter, Steffen Jung
No abstract text is available yet for this article.
January 19, 2017: Nature Immunology
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