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Nature Immunology

Arianne C Richard, Aaron T L Lun, Winnie W Y Lau, Berthold Göttgens, John C Marioni, Gillian M Griffiths
How cells respond to myriad stimuli with finite signaling machinery is central to immunology. In naive T cells, the inherent effect of ligand strength on activation pathways and endpoints has remained controversial, confounded by environmental fluctuations and intercellular variability within populations. Here we studied how ligand potency affected the activation of CD8+ T cells in vitro, through the use of genome-wide RNA, multi-dimensional protein and functional measurements in single cells. Our data revealed that strong ligands drove more efficient and uniform activation than did weak ligands, but all activated cells were fully cytolytic...
July 16, 2018: Nature Immunology
Paula Michea, Floriane Noël, Eve Zakine, Urszula Czerwinska, Philémon Sirven, Omar Abouzid, Christel Goudot, Alix Scholer-Dahirel, Anne Vincent-Salomon, Fabien Reyal, Sebastian Amigorena, Maude Guillot-Delost, Elodie Segura, Vassili Soumelis
The functions and transcriptional profiles of dendritic cells (DCs) result from the interplay between ontogeny and tissue imprinting. How tumors shape human DCs is unknown. Here we used RNA-based next-generation sequencing to systematically analyze the transcriptomes of plasmacytoid pre-DCs (pDCs), cell populations enriched for type 1 conventional DCs (cDC1s), type 2 conventional DCs (cDC2s), CD14+ DCs and monocytes-macrophages from human primary luminal breast cancer (LBC) and triple-negative breast cancer (TNBC)...
July 16, 2018: Nature Immunology
Greg Crawford, Mark David Hayes, Rocio Castro Seoane, Sophie Ward, Tim Dalessandri, Chester Lai, Eugene Healy, David Kipling, Charlotte Proby, Colin Moyes, Kile Green, Katie Best, Muzlifah Haniffa, Marina Botto, Deborah Dunn-Walters, Jessica Strid
IgE is an ancient and conserved immunoglobulin isotype with potent immunological function. Nevertheless, the regulation of IgE responses remains an enigma, and evidence of a role for IgE in host defense is limited. Here we report that topical exposure to a common environmental DNA-damaging xenobiotic initiated stress surveillance by γδTCR+ intraepithelial lymphocytes that resulted in class switching to IgE in B cells and the accumulation of autoreactive IgE. High-throughput antibody sequencing revealed that γδ T cells shaped the IgE repertoire by supporting specific variable-diversity-joining (VDJ) rearrangements with unique characteristics of the complementarity-determining region CDRH3...
July 16, 2018: Nature Immunology
Renu Balyan, Joanna Brzostek, Nicholas R J Gascoigne
No abstract text is available yet for this article.
July 16, 2018: Nature Immunology
J Michael McGraw, Wendy L Havran
No abstract text is available yet for this article.
July 16, 2018: Nature Immunology
Benedikt Rossboth, Andreas M Arnold, Haisen Ta, René Platzer, Florian Kellner, Johannes B Huppa, Mario Brameshuber, Florian Baumgart, Gerhard J Schütz
The main function of T cells is to identify harmful antigens as quickly and precisely as possible. Super-resolution microscopy data have indicated that global clustering of T cell antigen receptors (TCRs) occurs before T cell activation. Such pre-activation clustering has been interpreted as representing a potential regulatory mechanism that fine tunes the T cell response. We found here that apparent TCR nanoclustering could be attributed to overcounting artifacts inherent to single-molecule-localization microscopy...
July 16, 2018: Nature Immunology
Tri Giang Phan, Stuart G Tangye
No abstract text is available yet for this article.
July 9, 2018: Nature Immunology
Ryan H Newton, Sharad Shrestha, Jenna M Sullivan, Kathleen B Yates, Ewoud B Compeer, Noga Ron-Harel, Bruce R Blazar, Steven J Bensinger, W Nicholas Haining, Michael L Dustin, Daniel J Campbell, Hongbo Chi, Laurence A Turka
Foxo transcription factors play an essential role in regulating specialized lymphocyte functions and in maintaining T cell quiescence. Here, we used a system in which Foxo1 transcription-factor activity, which is normally terminated upon cell activation, cannot be silenced, and we show that enforcing Foxo1 activity disrupts homeostasis of CD4 conventional and regulatory T cells. Despite limiting cell metabolism, continued Foxo1 activity is associated with increased activation of the kinase Akt and a cell-intrinsic proliferative advantage; however, survival and cell division are decreased in a competitive setting or growth-factor-limiting conditions...
July 9, 2018: Nature Immunology
Munir Akkaya, Javier Traba, Alexander S Roesler, Pietro Miozzo, Billur Akkaya, Brandon P Theall, Haewon Sohn, Mirna Pena, Margery Smelkinson, Juraj Kabat, Eric Dahlstrom, David W Dorward, Jeff Skinner, Michael N Sack, Susan K Pierce
B cells are activated by two temporally distinct signals, the first provided by the binding of antigen to the B cell antigen receptor (BCR), and the second provided by helper T cells. Here we found that B cells responded to antigen by rapidly increasing their metabolic activity, including both oxidative phosphorylation and glycolysis. In the absence of a second signal, B cells progressively lost mitochondrial function and glycolytic capacity, which led to apoptosis. Mitochondrial dysfunction was a result of the gradual accumulation of intracellular calcium through calcium response-activated calcium channels that, for approximately 9 h after the binding of B cell antigens, was preventable by either helper T cells or signaling via the receptor TLR9...
July 9, 2018: Nature Immunology
Fiamma Salerno, Sander Engels, Maartje van den Biggelaar, Floris P J van Alphen, Aurelie Guislain, Wanqi Zhao, Deborah L Hodge, Sarah E Bell, Jan Paul Medema, Marieke von Lindern, Martin Turner, Howard A Young, Monika C Wolkers
Memory T cells are critical for the immune response to recurring infections. Their instantaneous reactivity to pathogens is empowered by the persistent expression of cytokine-encoding mRNAs. How the translation of proteins from pre-formed cytokine-encoding mRNAs is prevented in the absence of infection has remained unclear. Here we found that protein production in memory T cells was blocked via a 3' untranslated region (3' UTR)-mediated process. Germline deletion of AU-rich elements (AREs) in the Ifng-3' UTR led to chronic cytokine production in memory T cells...
July 9, 2018: Nature Immunology
Dimitris L Kontoyiannis
No abstract text is available yet for this article.
July 9, 2018: Nature Immunology
Wilson Castro, Sonia T Chelbi, Charlène Niogret, Cristina Ramon-Barros, Suzanne P M Welten, Kevin Osterheld, Haiping Wang, Giorgia Rota, Leonor Morgado, Eric Vivier, Miro E Raeber, Onur Boyman, Mauro Delorenzi, David Barras, Ping-Chih Ho, Annette Oxenius, Greta Guarda
Regulatory factor X 7 (Rfx7) is an uncharacterized transcription factor belonging to a family involved in ciliogenesis and immunity. Here, we found that deletion of Rfx7 leads to a decrease in natural killer (NK) cell maintenance and immunity in vivo. Genomic approaches showed that Rfx7 coordinated a transcriptional network controlling cell metabolism. Rfx7-/- NK lymphocytes presented increased size, granularity, proliferation, and energetic state, whereas genetic reduction of mTOR activity mitigated those defects...
July 2, 2018: Nature Immunology
Brandon Kwong, Rejane Rua, Yuanyuan Gao, John Flickinger, Yan Wang, Michael J Kruhlak, Jinfang Zhu, Eric Vivier, Dorian B McGavern, Vanja Lazarevic
In the version of this article initially published, in second paragraph of the second subsection of Results ('Peripheral licensing of CD4+ TH 17 cells in Tbx21-/- hosts'), the figure citation ('Fig. 1c') in the sentence that begins "In addition to" was incorrect. The correct citation is 'Fig. 1d'.
June 29, 2018: Nature Immunology
Zoltan Fehervari
In the version of this Research Highlight initially published, the url for the linked article was incorrect ( ). The correct link is . The error has been corrected in the HTML and PDF versions of the article.
June 28, 2018: Nature Immunology
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
In the version of this article initially published, the accession code for the RNA-seq data set deposited in the NCBI public repository Sequence Read Archive was missing from the 'Data availability' subsection of the Methods section. The accession code is SRP125477.
June 28, 2018: Nature Immunology
Laura Strauss, Nikolaos Patsoukis, Vassiliki A Boussiotis
In the version of this article initially published, the author surname citing the linked article (Miyama) was incorrect in the seventh and eighth paragraphs. The correct name is Miyajima.
June 28, 2018: Nature Immunology
Daisuke Aki, Hui Li, Wen Zhang, Mingke Zheng, Chris Elly, Jee H Lee, Weiguo Zou, Yun-Cai Liu
The mechanisms by which the sensitivity of naive CD4+ T cells to stimulation by the cognate antigen via the T cell antigen receptor (TCR) determines their differentiation into distinct helper T cell subsets remain elusive. Here we demonstrate functional collaboration of the ubiquitin E3 ligases Itch and WWP2 in regulating the strength of the TCR signal. Mice lacking both Itch and WWP2 in T cells showed spontaneous autoimmunity and lung inflammation. CD4+ T cells deficient in Itch and WWP2 exhibited hypo-responsiveness to TCR stimulation and a bias toward differentiation into the TH 2 subset of helper T cells...
June 20, 2018: Nature Immunology
Patrick Fernandes Rodrigues, Llucia Alberti-Servera, Anna Eremin, Gary E Grajales-Reyes, Robert Ivanek, Roxane Tussiwand
Plasmacytoid dendritic cells (pDCs) are an immune subset devoted to the production of high amounts of type 1 interferons in response to viral infections. Whereas conventional dendritic cells (cDCs) originate mostly from a common dendritic cell progenitor (CDP), pDCs have been shown to develop from both CDPs and common lymphoid progenitors. Here, we found that pDCs developed predominantly from IL-7R+ lymphoid progenitor cells. Expression of SiglecH and Ly6D defined pDC lineage commitment along the lymphoid branch...
June 20, 2018: Nature Immunology
(no author information available yet)
No abstract text is available yet for this article.
June 20, 2018: Nature Immunology
Markus G Manz
No abstract text is available yet for this article.
June 20, 2018: Nature Immunology
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