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Nature Immunology

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https://www.readbyqxmd.com/read/29035391/a-gammaherpesvirus-provides-protection-against-allergic-asthma-by-inducing-the-replacement-of-resident-alveolar-macrophages-with-regulatory-monocytes
#1
Bénédicte Machiels, Mickael Dourcy, Xue Xiao, Justine Javaux, Claire Mesnil, Catherine Sabatel, Daniel Desmecht, François Lallemand, Philippe Martinive, Hamida Hammad, Martin Guilliams, Benjamin Dewals, Alain Vanderplasschen, Bart N Lambrecht, Fabrice Bureau, Laurent Gillet
The hygiene hypothesis postulates that the recent increase in allergic diseases such as asthma and hay fever observed in Western countries is linked to reduced exposure to childhood infections. Here we investigated how infection with a gammaherpesvirus affected the subsequent development of allergic asthma. We found that murid herpesvirus 4 (MuHV-4) inhibited the development of house dust mite (HDM)-induced experimental asthma by modulating lung innate immune cells. Specifically, infection with MuHV-4 caused the replacement of resident alveolar macrophages (AMs) by monocytes with regulatory functions...
October 16, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28991267/cytotoxic-and-regulatory-roles-of-mucosal-associated-invariant-t-cells-in-type-1-diabetes
#2
Ophélie Rouxel, Jennifer Da Silva, Lucie Beaudoin, Isabelle Nel, Céline Tard, Lucie Cagninacci, Badr Kiaf, Masaya Oshima, Marc Diedisheim, Marion Salou, Alexandra Corbett, Jamie Rossjohn, James McCluskey, Raphael Scharfmann, Manuela Battaglia, Michel Polak, Olivier Lantz, Jacques Beltrand, Agnès Lehuen
Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of pancreatic β-cells by the immune system that involves innate and adaptive immune cells. Mucosal-associated invariant T cells (MAIT cells) are innate-like T-cells that recognize derivatives of precursors of bacterial riboflavin presented by the major histocompatibility complex (MHC) class I-related molecule MR1. Since T1D is associated with modification of the gut microbiota, we investigated MAIT cells in this pathology. In patients with T1D and mice of the non-obese diabetic (NOD) strain, we detected alterations in MAIT cells, including increased production of granzyme B, which occurred before the onset of diabetes...
October 9, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28967880/nlrx1-promotes-immediate-irf1-directed-antiviral-responses-by-limiting-dsrna-activated-translational-inhibition-mediated-by-pkr
#3
Hui Feng, Erik M Lenarcic, Daisuke Yamane, Eliane Wauthier, Jinyao Mo, Haitao Guo, David R McGivern, Olga González-López, Ichiro Misumi, Lola M Reid, Jason K Whitmire, Jenny P-Y Ting, Joseph A Duncan, Nathaniel J Moorman, Stanley M Lemon
NLRX1 is unique among the nucleotide-binding-domain and leucine-rich-repeat (NLR) proteins in its mitochondrial localization and ability to negatively regulate antiviral innate immunity dependent on the adaptors MAVS and STING. However, some studies have suggested a positive regulatory role for NLRX1 in inducing antiviral responses. We found that NLRX1 exerted opposing regulatory effects on viral activation of the transcription factors IRF1 and IRF3, which might potentially explain such contradictory results...
October 2, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28945245/identification-of-lineage-specifying-cytokines-that-signal-all-cd8-cytotoxic-lineage-fate-decisions-in-the-thymus
#4
Ruth Etzensperger, Tejas Kadakia, Xuguang Tai, Amala Alag, Terry I Guinter, Takeshi Egawa, Batu Erman, Alfred Singer
T cell antigen receptor (TCR) signaling in the thymus initiates positive selection, but the CD8(+)-lineage fate is thought to be induced by cytokines after TCR signaling has ceased, although this remains controversial and unproven. We have identified four cytokines (IL-6, IFN-γ, TSLP and TGF-β) that did not signal via the common γ-chain (γc) receptor but that, like IL-7 and IL-15, induced expression of the lineage-specifying transcription factor Runx3d and signaled the generation of CD8(+) T cells. Elimination of in vivo signaling by all six of these 'lineage-specifying cytokines' during positive selection eliminated Runx3d expression and completely abolished the generation of CD8(+) single-positive thymocytes...
September 25, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28945244/human-antibodies-to-the-dengue-virus-e-dimer-epitope-have-therapeutic-activity-against-zika-virus-infection
#5
Estefania Fernandez, Wanwisa Dejnirattisai, Bin Cao, Suzanne M Scheaffer, Piyada Supasa, Wiyada Wongwiwat, Prabagaran Esakky, Andrea Drury, Juthathip Mongkolsapaya, Kelle H Moley, Indira U Mysorekar, Gavin R Screaton, Michael S Diamond
The Zika virus (ZIKV) epidemic has resulted in congenital abnormalities in fetuses and neonates. Although some cross-reactive dengue virus (DENV)-specific antibodies can enhance ZIKV infection in mice, those recognizing the DENV E-dimer epitope (EDE) can neutralize ZIKV infection in cell culture. We evaluated the therapeutic activity of human monoclonal antibodies to DENV EDE for their ability to control ZIKV infection in the brains, testes, placentas, and fetuses of mice. A single dose of the EDE1-B10 antibody given 3 d after ZIKV infection protected against lethality, reduced ZIKV levels in brains and testes, and preserved sperm counts...
September 25, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28945243/germline-bias-dictates-cross-serotype-reactivity-in-a-common-dengue-virus-specific-cd8-t-cell-response
#6
Abigail Culshaw, Kristin Ladell, Stephanie Gras, James E McLaren, Kelly L Miners, Carine Farenc, Heleen van den Heuvel, Emma Gostick, Wanwisa Dejnirattisai, Apirath Wangteeraprasert, Thaneeya Duangchinda, Pojchong Chotiyarnwong, Wannee Limpitikul, Sirijitt Vasanawathana, Prida Malasit, Tao Dong, Jamie Rossjohn, Juthathip Mongkolsapaya, David A Price, Gavin R Screaton
Adaptive immune responses protect against infection with dengue virus (DENV), yet cross-reactivity with distinct serotypes can precipitate life-threatening clinical disease. We found that clonotypes expressing the T cell antigen receptor (TCR) β-chain variable region 11 (TRBV11-2) were 'preferentially' activated and mobilized within immunodominant human-leukocyte-antigen-(HLA)-A*11:01-restricted CD8(+) T cell populations specific for variants of the nonstructural protein epitope NS3133 that characterize the serotypes DENV1, DENV3 and DENV4...
September 25, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28920951/srebp-controlled-glucose-metabolism-is-essential-for-nk-cell-functional-responses
#7
Nadine Assmann, Katie L O'Brien, Raymond P Donnelly, Lydia Dyck, Vanessa Zaiatz-Bittencourt, Róisín M Loftus, Paul Heinrich, Peter J Oefner, Lydia Lynch, Clair M Gardiner, Katja Dettmer, David K Finlay
Activated natural killer (NK) cells engage in a robust metabolic response that is required for normal effector function. Using genetic, pharmacological and metabolic analyses, we demonstrated an essential role for Srebp transcription factors in cytokine-induced metabolic reprogramming of NK cells that was independent of their conventional role in the control of lipid synthesis. Srebp was required for elevated glycolysis and oxidative phosphorylation and promoted a distinct metabolic pathway configuration in which glucose was metabolized to cytosolic citrate via the citrate-malate shuttle...
September 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28892471/dynamic-regulation-of-t-follicular-regulatory-cell-responses-by-interleukin-2-during-influenza-infection
#8
Davide Botta, Michael J Fuller, Tatiana T Marquez-Lago, Holly Bachus, John E Bradley, Amy S Weinmann, Allan J Zajac, Troy D Randall, Frances E Lund, Beatriz León, André Ballesteros-Tato
Interleukin 2 (IL-2) promotes Foxp3(+) regulatory T (Treg) cell responses, but inhibits T follicular helper (TFH) cell development. However, it is not clear how IL-2 affects T follicular regulatory (TFR) cells, a cell type with properties of both Treg and TFH cells. Using an influenza infection model, we found that high IL-2 concentrations at the peak of the infection prevented TFR cell development by a Blimp-1-dependent mechanism. However, once the immune response resolved, some Treg cells downregulated CD25, upregulated Bcl-6 and differentiated into TFR cells, which then migrated into the B cell follicles to prevent the expansion of self-reactive B cell clones...
September 11, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28892470/different-molecular-complexes-that-mediate-transcriptional-induction-and-repression-by-foxp3
#9
Ho-Keun Kwon, Hui-Min Chen, Diane Mathis, Christophe Benoist
FoxP3 conditions the transcriptional signature and functional facets of regulatory T cells (Treg cells). Its mechanism of action, whether as an activator or a repressor, has remained unclear. Here, chromatin analysis showed that FoxP3 bound active enhancer elements, not repressed chromatin, around loci over- or under-expressed in Treg cells. We evaluated the impact of a panel of FoxP3 mutants on its transcriptional activity and interactions with DNA, transcriptional cofactors and chromatin. Computational integration, confirmed by biochemical interaction and size analyses, showed that FoxP3 existed in distinct multimolecular complexes...
September 11, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28892469/de-novo-induction-of-intratumoral-lymphoid-structures-and-vessel-normalization-enhances-immunotherapy-in-resistant-tumors
#10
Anna Johansson-Percival, Bo He, Zhi-Jie Li, Alva Kjellén, Karen Russell, Ji Li, Irma Larma, Ruth Ganss
The tumor microenvironment confers profound resistance to anti-cancer immunotherapy. By targeting LIGHT, a member of the TNF superfamily of cytokines, to tumor vessels via a vascular targeting peptide (VTP), we developed a reagent with the dual ability to modulate the angiogenic vasculature and to induce tertiary lymphoid structures (TLSs). LIGHT-VTP triggered the influx of endogenous T cells into autochthonous or syngeneic tumors, which are resistant to immunotherapy. LIGHT-VTP in combination with checkpoint inhibition generated a large number of intratumoral effector and memory T cells with ensuing survival benefits, while the addition of anti-tumor vaccination achieved maximal therapeutic efficacy...
September 11, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28846086/the-rna-helicase-ddx46-inhibits-innate-immunity-by-entrapping-m-6-a-demethylated-antiviral-transcripts-in-the-nucleus
#11
Qingliang Zheng, Jin Hou, Ye Zhou, Zhenyang Li, Xuetao Cao
DEAD-box (DDX) helicases are vital for the recognition of RNA and metabolism and are critical for the initiation of antiviral innate immunity. Modification of RNA is involved in many biological processes; however, its role in antiviral innate immunity has remained unclear. Here we found that nuclear DDX member DDX46 inhibited the production of type I interferons after viral infection. DDX46 bound Mavs, Traf3 and Traf6 transcripts (which encode signaling molecules involved in antiviral responses) via their conserved CCGGUU element...
October 2017: Nature Immunology
https://www.readbyqxmd.com/read/28846085/a-two-amino-acid-substitution-in-the-transcription-factor-ror%C3%AE-t-disrupts-its-function-in-th17-differentiation-but-not-in-thymocyte-development
#12
Zhiheng He, Jian Ma, Ruiqing Wang, Jing Zhang, Zhaofeng Huang, Fei Wang, Subha Sen, Ellen V Rothenberg, Zuoming Sun
The transcription factor RORγt regulates differentiation of the TH17 subset of helper T cells, thymic T cell development and lymph-node genesis. Although elimination of RORγt prevents TH17 cell-mediated experimental autoimmune encephalomyelitis (EAE), it also disrupts thymocyte development, which could lead to lethal thymic lymphoma. Here we identified a two-amino-acid substitution in RORγt (RORγt(M)) that 'preferentially' disrupted TH17 differentiation but not thymocyte development. Mice expressing RORγt(M) were resistant to EAE associated with defective TH17 differentiation but maintained normal thymocyte development and normal lymph-node genesis, except for Peyer's patches...
October 2017: Nature Immunology
https://www.readbyqxmd.com/read/28846084/ifn-%C3%AE-suppresses-intestinal-inflammation-by-non-translational-regulation-of-neutrophil-function
#13
Achille Broggi, Yunhao Tan, Francesca Granucci, Ivan Zanoni
Interferon-λ (IFN-λ) is a central regulator of mucosal immunity; however, its signaling specificity relative to that of type I interferons is poorly defined. IFN-λ can induce antiviral interferon-stimulated genes (ISGs) in epithelia, while the effect of IFN-λ in non-epithelial cells remains unclear. Here we report that neutrophils responded to IFN-λ. We found that in addition to inducing ISG transcription, IFN-λ (but not IFN-β) specifically activated a translation-independent signaling pathway that diminished the production of reactive oxygen species and degranulation in neutrophils...
October 2017: Nature Immunology
https://www.readbyqxmd.com/read/28825702/asynchronous-lineage-priming-determines-commitment-to-t-cell-and-b-cell-lineages-in-fetal-liver
#14
Claire Berthault, Cyrille Ramond, Odile Burlen-Defranoux, Guillaume Soubigou, Sylvestre Chea, Rachel Golub, Pablo Pereira, Paulo Vieira, Ana Cumano
The molecular events that initiate lymphoid-lineage specification remain unidentified because the stages of differentiation during which lineage commitment occurs are difficult to characterize. We isolated fetal liver progenitor cells undergoing restriction of their differentiation potential toward the T cell-innate lymphoid cell lineage or the B cell lineage. Transcripts that defined the molecular signatures of these two subsets were sequentially upregulated in lympho-myeloid precursor cells and in common lymphoid progenitor cells, respectively, and this preceded lineage restriction; this indicates that T cell-versus-B cell commitment is not a binary fate 'decision'...
October 2017: Nature Immunology
https://www.readbyqxmd.com/read/28825701/type-i-interferons-and-the-cytokine-tnf-cooperatively-reprogram-the-macrophage-epigenome-to-promote-inflammatory-activation
#15
Sung Ho Park, Kyuho Kang, Eugenia Giannopoulou, Yu Qiao, Keunsoo Kang, Geonho Kim, Kyung-Hyun Park-Min, Lionel B Ivashkiv
Cross-regulation of Toll-like receptor (TLR) responses by cytokines is essential for effective host defense, avoidance of toxicity and homeostasis, but the underlying mechanisms are not well understood. Our comprehensive epigenomics approach to the analysis of human macrophages showed that the proinflammatory cytokines TNF and type I interferons induced transcriptional cascades that altered chromatin states to broadly reprogram responses induced by TLR4. TNF tolerized genes encoding inflammatory molecules to prevent toxicity while preserving the induction of genes encoding antiviral and metabolic molecules...
October 2017: Nature Immunology
https://www.readbyqxmd.com/read/28805812/t-bet-dependent-nkp46-innate-lymphoid-cells-regulate-the-onset-of-th17-induced-neuroinflammation
#16
Brandon Kwong, Rejane Rua, Yuanyuan Gao, John Flickinger, Yan Wang, Michael J Kruhlak, Jinfang Zhu, Eric Vivier, Dorian B McGavern, Vanja Lazarevic
The transcription factor T-bet has been associated with increased susceptibility to systemic and organ-specific autoimmunity, but the mechanism by which T-bet expression promotes neuroinflammation remains unknown. In this study, we demonstrate a cardinal role of T-bet-dependent NKp46(+) innate lymphoid cells (ILCs) in the initiation of CD4(+) TH17-mediated neuroinflammation. Loss of T-bet specifically in NKp46(+) ILCs profoundly impaired the ability of myelin-reactive TH17 cells to invade central nervous system (CNS) tissue and protected the mice from autoimmunity...
October 2017: Nature Immunology
https://www.readbyqxmd.com/read/28805811/caveolin-1-dependent-nanoscale-organization-of-the-bcr-regulates-b-cell-tolerance
#17
Susana Minguet, Kathrin Kläsener, Anna-Maria Schaffer, Gina J Fiala, Teresa Osteso-Ibánez, Katrin Raute, Inmaculada Navarro-Lérida, Frederike A Hartl, Maximilian Seidl, Michael Reth, Miguel A Del Pozo
Caveolin-1 (Cav1) regulates the nanoscale organization and compartmentalization of the plasma membrane. Here we found that Cav1 controlled the distribution of nanoclusters of isotype-specific B cell antigen receptors (BCRs) on the surface of B cells. In mature B cells stimulated with antigen, the immunoglobulin M BCR (IgM-BCR) gained access to lipid domains enriched for GM1 glycolipids, by a process that was dependent on the phosphorylation of Cav1 by the Src family of kinases. Antigen-induced reorganization of nanoclusters of IgM-BCRs and IgD-BCRs regulated BCR signaling in vivo...
October 2017: Nature Immunology
https://www.readbyqxmd.com/read/28783152/genome-wide-dna-methylation-landscape-defines-specialization-of-regulatory-t-cells-in-tissues
#18
Michael Delacher, Charles D Imbusch, Dieter Weichenhan, Achim Breiling, Agnes Hotz-Wagenblatt, Ulrike Träger, Ann-Cathrin Hofer, Danny Kägebein, Qi Wang, Felix Frauhammer, Jan-Philipp Mallm, Katharina Bauer, Carl Herrmann, Philipp A Lang, Benedikt Brors, Christoph Plass, Markus Feuerer
Regulatory T cells (Treg cells) perform two distinct functions: they maintain self-tolerance, and they support organ homeostasis by differentiating into specialized tissue Treg cells. We found that epigenetic modifications defined the molecular characteristics of tissue Treg cells. Tagmentation-based whole-genome bisulfite sequencing revealed more than 11,000 regions that were methylated differentially in pairwise comparisons of tissue Treg cell populations and lymphoid T cells. Similarities in the epigenetic landscape led to the identification of a common tissue Treg cell population that was present in many organs and was characterized by gain and loss of DNA methylation that included many gene sites associated with the TH2 subset of helper T cells, such as the gene encoding cytokine IL-33 receptor ST2, as well as the production of tissue-regenerative factors...
October 2017: Nature Immunology
https://www.readbyqxmd.com/read/28926546/-t-betting-on-innate-lymphoid-cells-in-cns-inflammatory-disease
#19
Melissa A Brown, Abigail E Russi
No abstract text is available yet for this article.
September 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28926545/generating-cd4-cd8%C3%AE-%C3%AE-iels
#20
Laurie A Dempsey
No abstract text is available yet for this article.
September 19, 2017: Nature Immunology
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