Nature Immunology Contents: May 2016 Volume 17 pp 471 - 603

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Advertisement NEW WHITE PAPER: The Latest Advances in Cell and Tissue Engrafted Mice  This white paper provides an in-depth overview of mice engrafted with human cells and tissues and how they can help to bridge the biological gap between mice and humans.  Learn More About: How cell and tissue engrafted mice are generated The application of immune system engrafted models in basic and applied research And, read an evaluation of the available super immunodeficient models for cell and issue Download Your Copy Today TABLE OF CONTENTS May 2016 Volume 17, Issue 5 Correspondence News and Views Research Highlights Perspectives Articles Advertisement nature.com webcasts Nature Publishing Group presents a custom webcast on: Releasable purification of monocytes for human dendritic cell generation Wednesday April 27, 2016 8AM PDT, 11AM EDT, 4PM BST, 5PM CEST   Register for the webcast and live Q&A session    Sponsored by: Quad Technologies Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Tumor Immunology and Immunotherapy Join us October 20-23, 2016 in Boston, MA for an exchange of ideas on strategies to harness the immune system for the treatment and prevention of different cancers. http://www.AACR.org/TII   Advertisement npj Vaccines is an online-only, open access, multidisciplinary journal dedicated to publishing cutting-edge research and development on human and veterinary vaccines. npj Vaccines is now open for submissions – explore the benefits of submitting your next manuscript to the journal.   Advertisement THE GENOMICS OF COMMON DISEASES 2016  Presented by Nature Genetics in association with the Wellcome Trust September 25-28, 2016 Renaissance Baltimore Harborplace Hotel | Baltimore, MD, USA REGISTER NOW!   Correspondence Top Spontaneous partial loss of the OT-I transgene   p471 Gretchen Harms Pritchard, Eric W Cross, Marjorie Strobel, Stephen C Jameson, Ross M Kedl et al. doi:10.1038/ni.3411 News and Views Top A human inborn error connects the α's   pp472 - 474 Isabelle Meyts and Jean-Laurent Casanova doi:10.1038/ni.3420 Patients with XLPDR are found to carry an intronic hypomorphic mutation in the gene encoding the catalytic subunit of DNA polymerase-α. Patients' cells display low levels of cytoplasmic RNA:DNA hybrids, which increases the expression of interferon-α-induced genes, a hallmark of monogenic 'type I interferonopathies'. See also: Article by Starokadomskyy et al. A dendritic cell subset designed for oral tolerance   pp474 - 476 Reinhard Hinterleitner and Bana Jabri doi:10.1038/ni.3435 Studies using genetic tools have identified the distinct dendritic cell subsets that ensure tolerance to oral antigens in the antigen-rich environment of the gut and suggest a 'division of labor' for protective immunity. See also: Article by Esterházy et al. Tumor-necrosis factor is a master of T cell exhaustion   pp476 - 478 Amy E Baxter and Daniel E Kaufmann doi:10.1038/ni.3436 Chronic viral infections are characterized by ongoing inflammation and a dysfunctional T cell response, which results in a failure of the host to clear the pathogen. Now these two hallmarks of infection have been linked by the classic pro-inflammatory cytokine tumor-necrosis factor. See also: Article by Beyer et al. PP2A's restraint of mTOR is critical for Treg cell activity   pp478 - 479 Greg M Delgoffe doi:10.1038/ni.3442 Regulatory T cells must limit activation of the metabolic checkpoint kinase mTOR to maintain their identity. The lipid ceramide serves a unique role in this process by inducing phosphatase PP2A-mediated inhibition of the mTORC1 complex. See also: Article by Apostolidis et al. Immunology JOBS of the week Faculty Positions in Immunology ~ Dana-Farber / Harvard Medical School Dana-Farber Cancer Institute & Harvard medical School Tier 2 Canada Research Chair in Human Immunology and Inflammation Dalhousie University Post-doctoral Research Fellow – Dormancy / Immunology Fred Hutchinson Cancer Research Center Faculty Position in Tumor Immunology Northwestern University Faculty Positions in Cancer Immunology University of New Mexico More Science jobs from Immunology EVENT International Conference on Human & Translational Immunology 16th Sept - 21st Sept 2016 Rhodes, Greece More science events from Research Highlights Top Myeloid dysfunction in ALS | Good cholesterol | Club cells to the rescue | Gender imbalance | Platelet bias with age | Beyond systems analysis Perspectives Top Interferon-induced guanylate-binding proteins in inflammasome activation and host defense   pp481 - 489 Bae-Hoon Kim, Jonathan D Chee, Clinton J Bradfield, Eui-Soon Park, Pradeep Kumar et al. doi:10.1038/ni.3440 In this Perspective, MacMicking and colleagues discuss the roles of interferon-induced guanylate-binding proteins in directing inflammasome responses and their effects on immunity to a wide variety of microbial pathogens. Parallels and differences between innate and adaptive lymphocytes   pp490 - 494 Sammy Bedoui, Thomas Gebhardt, Georg Gasteiger and Wolfgang Kastenmüller doi:10.1038/ni.3432 Bedoui and colleagues discuss the naive state of conventional T cells as an actively repressed condition that supports T cell diversity and enables the flexible differentiation of effectors, and also offers a relevant discrimination criterion between innate and adaptive lymphocytes. Articles Top DNA polymerase-α regulates the activation of type I interferons through cytosolic RNA:DNA synthesis   pp495 - 504 Petro Starokadomskyy, Terry Gemelli, Jonathan J Rios, Chao Xing, Richard C Wang et al. doi:10.1038/ni.3409 The causative mechanism for the immunodeficiency and autoinflammatory disease XLPDR is unknown. Burstein and colleagues show that XLPDR is caused by disruption of POLA1, which encodes a DNA polymerase subunit; this, in turn, leads to dysregulated production of type I interferons. See also: News and Views by Meyts & Casanova Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease   pp505 - 513 Nathan D Mathewson, Robert Jenq, Anna V Mathew, Mark Koenigsknecht, Alan Hanash et al. doi:10.1038/ni.3400 Irradiation to condition hosts for bone marrow transplantation leads to alterations in intestinal microbiota. Reddy and colleagues demonstrate that these changes result in reduced butyrate production and breakdown of intestinal barrier function. S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3   pp514 - 522 Fuan Wang, Tommy Alain, Kristy J Szretter, Kyle Stephenson, Jonathan G Pol et al. doi:10.1038/ni.3433 Activation of the transcription factor IRF3 is a key event in antiviral responses. Lichty and colleagues show that recruitment of the mTOR downstream effector S6K1 to the STING-TBK1 signaling complex is required for the activation of IRF3 after infection with DNA viruses. A phosphomimetic-based mechanism of dengue virus to antagonize innate immunity   pp523 - 530 Ying Kai Chan and Michaela U Gack doi:10.1038/ni.3393 14-3-3ϵ serves a crucial function in antiviral immunity by mediating the translocation of RIG-I from the cytosol to mitochondria. Chan and Gack have found that the NS3 protein of Dengue virus binds to 14-3-3ϵ via a highly conserved phosphomimetic motif and thereby blocks RIG-I translocation and antiviral signaling. The intracellular pathway for the presentation of vitamin B-related antigens by the antigen-presenting molecule MR1   pp531 - 537 Hamish E G McWilliam, Sidonia B G Eckle, Alex Theodossis, Ligong Liu, Zhenjun Chen et al. doi:10.1038/ni.3416 MR1 molecules present bacterial metabolites to MAIT innate lymphocytes, but the processing and presentation pathway of these ligands are unclear. McCluskey, Rossjohn, Villadangos and colleagues demonstrate that MR1 ligands bind in the ER, which initiates trafficking to the plasma membrane and subsequent presentation. Acidic chitinase primes the protective immune response to gastrointestinal nematodes   pp538 - 544 Kevin M Vannella, Thirumalai R Ramalingam, Kevin M Hart, Rafael de Queiroz Prado, Joshua Sciurba et al. doi:10.1038/ni.3417 The physiological function of the mammalian chitinase AMCase is unclear. Wynn and colleagues show that it is dispensable for allergic lung inflammation but is necessary for clearance of intestinal helminths. Classical dendritic cells are required for dietary antigen-mediated induction of peripheral Treg cells and tolerance   pp545 - 555 Daria Esterházy, Jakob Loschko, Mariya London, Veronica Jove, Thiago Y Oliveira et al. doi:10.1038/ni.3408 The subsets of antigen presenting cells (APCs) that mediate tolerance to oral antigens remain unclear. Mucida and colleagues use lineage-specific depletion of APCs to show that monocyte-derived APCs are dispensable, while classical dendritic cells are critical, for the induction of regulatory T cells and oral tolerance. See also: News and Views by Hinterleitner & Jabri Phosphatase PP2A is requisite for the function of regulatory T cells   pp556 - 564 Sokratis A Apostolidis, Noé Rodríguez-Rodríguez, Abel Suárez-Fueyo, Nikolina Dioufa, Esra Ozcan et al. doi:10.1038/ni.3390 Regulatory T cells use a distinct metabolism to exert their regulatory function. Tsokos and colleagues show that the phosphatase PP2A suppresses the metabolic-checkpoint kinase complex mTORC1 in these cells and is necessary for their function. PP2A activity is regulated by the cellular abundance of ceramide via a transcription factor Foxp3-dependent feedback mechanism. See also: News and Views by Delgoffe Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling   pp565 - 573 Yan Xing, Xiaodan Wang, Stephen C Jameson and Kristin A Hogquist doi:10.1038/ni.3419 Positively selected thymocytes require a maturation phase before emigrating from the thymus. Hogquist and colleagues show that functional maturation is driven by tonic signals provided by type I interferons and the transcription factor NF-κB. Initiation of T cell signaling by CD45 segregation at 'close contacts'   pp574 - 582 Veronica T Chang, Ricardo A Fernandes, Kristina A Ganzinger, Steven F Lee, Christian Siebold et al. doi:10.1038/ni.3392 The receptor tyrosine phosphatase CD45 has an important role in T cell activation. Davis and colleagues resolve the structure of CD45 and provide molecular insights into how it contributes to productive T cell receptor triggering. T cell-intrinsic ASC critically promotes TH17-mediated experimental autoimmune encephalomyelitis   pp583 - 592 Bradley N Martin, Chenhui Wang, Cun-jin Zhang, Zizhen Kang, Muhammet Fatih Gulen et al. doi:10.1038/ni.3389 Inflammasome activation triggers the release of active interleukin 1β (IL-1β). Li and colleagues show that TH17 cells can release IL-1β upon T cell antigen receptor and ATP stimulation via an ASC-NLPR3-caspase-8 axis, thereby contributing to neuroinflammation. Tumor-necrosis factor impairs CD4+ T cell-mediated immunological control in chronic viral infection   pp593 - 603 Marc Beyer, Zeinab Abdullah, Jens M Chemnitz, Daniela Maisel, Jil Sander et al. doi:10.1038/ni.3399 Functional T cell exhaustion occurs during chronic viral infection or in tumor settings. Beyer et al. report that chronic inflammation mediated by the cytokine TNF is responsible for this dysfunction and that blockade of this pathway restores immune system-mediated control of viral infection. See also: News and Views by Baxter & Kaufmann Top Advertisement Emerging Microbes & Infections is an open access, peer-review journal providing an integrated forum to allow for the timely dissemination of large amount of information gathered about microbes and infections, especially ones associated with increasing biological and clinical significance and pathogenic frequency.  Submit your manuscript   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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