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Pulmonary Cell News| Immune Regulation News 9.22 June 16, 2017 | |
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TOP STORYMicroglia-Dependent Synapse Loss in Type I Interferon-Mediated Lupus Scientists report behavioral phenotypes and synapse loss in lupus-prone mice that are prevented by blocking type I interferon (IFN) signaling. They showed that type I IFN stimulated microglia to become reactive and engulf neuronal and synaptic material in lupus-prone mice. [Nature] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)Local Amplifiers of IL-4Rα–Mediated Macrophage Activation Promote Repair in Lung and Liver Investigators have discovered local tissue-specific amplifiers of type 2–mediated macrophage activation. In the lung, surfactant protein A enhanced interleukin-4 (IL-4)–dependent macrophage proliferation and activation, accelerating parasite clearance and reducing pulmonary injury after infection with a lung-migrating helminth. [Science] Abstract Elimination of Large Tumors in Mice by mRNA-Encoded Bispecific Antibodies The potential of bispecific T cell–engaging antibodies is hindered by manufacturing challenges and short serum half-life. The authors circumvented these limitations by treating mice with in vitro–transcribed pharmacologically optimized, nucleoside-modified mRNA encoding the antibody. They achieved sustained endogenous synthesis of the antibody, which eliminated advanced tumors as effectively as the corresponding purified bispecific antibody. [Nat Med] Abstract Exploiting Macrophage Autophagy-Lysosomal Biogenesis as a Therapy for Atherosclerosis Plaque progression renders macrophages unable to degrade exogenous atherogenic material and endogenous cargo including dysfunctional proteins and organelles. Scientists showed that a decline in the autophagy–lysosome system contributes to this as evidenced by a derangement in key autophagy markers in both mouse and human atherosclerotic plaques. [Nat Commun] Full Article Lkb1 Maintains Treg Cell Lineage Identity The authors showed that Lkb1 maintains Treg cell lineage identity by stabilizing Foxp3 expression and enforcing suppressor function. Upon T-cell receptor stimulation Lkb1 protein expression is upregulated in Treg cells but not in conventional T cells. Mice with Treg cell-specific deletion of Lkb1 develop a fatal early-onset autoimmune disease, with no Foxp3 expression in most Treg cells. [Nat Commun] Full Article SUMO-Triggered Ubiquitination of NR4A1 Controls Macrophage Cell Death Investigators showed that nuclear receptor NR4A1 is sumoylated by SUMO2/3. Upon poly-SUMO modification, NR4A1 can be targeted by the SUMO-dependent E3 ubiquitin ligase RNF4 for polyubiquitination and subsequent degradation. [Cell Death Differ] Abstract Researchers report that environmental conditions resulting in cellular stress, such as low oxygen, glucose, and isotonic stress, particularly enhance the generation of T helper-17 (Th17) cells. Pharmacological inhibition of cell stress reduces Th17 cell differentiation while stress inducers enhance the development of Th17 cells. The cellular stress response results in Th17 cell development via sustained cytoplasmic calcium levels and, in part, XBP1 activity. [Cell Rep] Abstract | Full Article | Graphical Abstract miRNA Profiling during Antigen-Dependent T Cell Activation: A Role for miR-132-3p Investigators analyzed the changes of the miRNA profiles of T cells in response to activation by cognate interaction with dendritic cells. They also studied mRNA targets common to miRNAs regulated in T cell activation. pik3r1 gene, which encodes the regulatory subunits of PI3K p50, p55 and p85, was identified as target of miRNAs upregulated after T cell activation. [Sci Rep] Full Article APC-Targeted Proinsulin Expression Inactivates Insulin-Specific Memory CD8+ T Cells in NOD Mice Targeting antigen expression to antigen-presenting cells inactivates cognate CD8+ effector and memory T-cell responses and has therapeutic potential. Scientists investigated this in the context of insulin-specific responses in the non-obese diabetic mouse where genetic immune tolerance defects could impact on therapeutic tolerance induction. [Immunol Cell Biol] Abstract Murine LRBA-Deficiency Causes CTLA-4 Deficiency in Tregs without Progression to Immune Dysregulation To understand the pathogenesis of common variable immunodeficiency. C57BL/6 mice carrying a homozygous truncating mutation in lipopolysaccharide responsive beige-like anchor (LRBA) were produced using CRISPR/Cas9-mediated gene targeting. These mice revealed that LRBA plays a critical, cell autonomous role in promoting CTLA-4 accumulation within CD4 effector T cells and FOXP3+ T regulatory cells. [Immunol Cell Biol] Abstract | Full Article Subscribe to our sister publications: Human Immunology News & Immunology of Infectious Disease News. | |
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REVIEWSQuantitative Imaging Approaches to Study the CAR Immunological Synapse The authors review the formation of the lytic immunological synapse and describe quantitative imaging-based measurements using multiple microscopy techniques at a single cell level that can be used in conjunction with established population-based assays to provide insight into the important cytotoxic function of chimeric antigen receptor (CAR) cells. [Mol Ther] Abstract | Graphical Abstract Visit our reviews page to see a complete list of reviews in the immune regulation research field. | |
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SCIENCE NEWSSeattle Genetics, Inc. and Bristol-Myers Squibb Company highlighted an updated interim analysis from the ongoing Phase I/II clinical trial evaluating ADCETRIS and Opdivo in relapsed or refractory classical Hodgkin lymphoma. [Press release from Seattle Genetics, Inc. discussing research presented at the International Conference on Malignant Lymphoma (ICML), Lugano] Press Release OSE Immunotherapeutics SA presented new data for OSE-127, an antagonist of the interleukin-7 receptor (IL-7R). The communication entitled “IL-7 pathway controls human T cell homing to the gut and culminates in inflammatory bowel disease mucosa” showed efficacy results for OSE-127 in various preclinical acute or chronic colitis models and ex vivo human biopsies. [Press release from OSE Immunotherapeutics SA discussing research presented at the Federation of Clinical Immunology Societies (FOCIS), Chicago] Press Release | |
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INDUSTRY NEWSIntegral Molecular has initiated a therapeutic target discovery program in immuno-oncology by exploiting its membrane proteome array technology to identify cell-surface proteins involved in regulating the ability of the human immune system to recognize and destroy cancer. [Integral Molecular] Press Release Generon Corporation announced the initiation of a clinical trial for A-337, a CD3-activating bi-specific antibody targeting EpCAM, in Australia. This is a phase I, open-label, dose-escalation study to evaluate the safety and pharmacokinetics of A-337 in patients with advanced solid tumors. EpCAM is up-regulated and over-expressed in most solid tumors. [Generon Corporation] Press Release MaxCyte Inc. announced it has entered into a Cooperative Research and Development Agreement with the National Institutes of Health’s National Institute of Allergy and Infectious Diseases to develop treatments for X-linked chronic granulomatous disease using next-generation gene correction leveraging CRISPR/Cas9 and MaxCyte’s Flow Electroporationâ„¢ Platform. [MaxCyte Inc.] Press Release AbbVie and Principia Announce Collaboration on Oral Immunoproteasome Inhibitors AbbVie and Principia Biopharma Inc. announced that they have entered a collaboration for the development of oral immunoproteasome inhibitors. The collaboration is aimed at developing first-in-class oral therapies that bring the power of proteasome inhibition safely into the field of immunology. [AbbVie] Press Release OSE Immunotherapeutics SA announced that the company has entered into a multi-year research collaboration on OSE-703, a cytotoxic monoclonal antibody against the alpha chain of interleukin-7 receptor (IL-7R), with Memorial Sloan Kettering Cancer Center in New York. [OSE Immunotherapeutics SA] Press Release Intellia Therapeutics and San Raffaele University and Research Hospital have entered into a three-year research collaboration, option and license agreement to engineer optimized T cell cancer therapies. [Intellia Therapeutics, Inc.] Press Release Dragonfly Therapeutics, Inc. announced a global strategic collaboration with Celgene Corporation and its affiliates to discover, develop and commercialize innovative immuno-oncology treatment options for patients with hematological malignancies based on Dragonfly’s NK cell based TriNKETâ„¢ technology platform. [Dragonfly Therapeutics, Inc. (PR Newswire Association LLC.)] Press Release | |
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POLICY NEWSBiologists Debate How to License Preprints Biology’s zeal for preprints — papers posted online before peer review — is opening up a thorny legal debate: should scientists license their manuscripts on open-access terms? Researchers have now shared more than 11,000 papers at the popular bioRxiv preprints site. But where some researchers allow their bioRxiv manuscripts to be freely redistributed and reused, others have chosen to lock them down with restrictive terms. [Nature News] Editorial Indian Research Labs Face Financial Crisis India’s 38 premier scientific laboratories are in a budgetary pinch. A jump in expenditures on salaries, pensions, and perks for government employees, recommended by an advisory commission, is leaving little money for new research in the budget of the Council of Scientific & Industrial Research, based in New Delhi, which oversees the labs and their 4600 scientists. [ScienceInsider] Editorial Empty Rhetoric over Data Sharing Slows Science Government agencies lack the funds to build platforms for data sharing and resist taking responsibility for such infrastructure. They may hope that universities will host data, but the development of institutional repositories is patchy, and to rely on them is effectively to discourage common data standards and curation. [Nature News] Editorial
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EVENTSNEW AACR-NCI-EORTC Molecular Targets & Cancer Therapeutics NEW American College of Allergy, Asthma, & Immunology (ACAAI) Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Research Scientist – Immunogenomics (University of Oxford) Scientific Sales Representative – Cell Separation (STEMCELL Technologies Inc.) Scientist – Neuroinflammation (University Health Network) Postdoctoral Fellow – Neuroimmunology (The University of Texas MD Anderson Cancer Center) Immunologist – Brain Cancer (Columbia University) Postdoctoral Position – Cancer Immunology and Immunotherapy (Weill Cornell Medicine) Scientist I – T Cell Immunology (Celgene Corporation) Scientist – Analytical Development (KBI Biopharma) Senior Scientist – Molecular and Cellular Neuroimmunology (Pfizer) Principal Scientist – Immuno Oncology (Celgene Corporation) Assistant Associate or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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Home Immune Regulation News Volume 9.22 | Jun 16 2017
