Volume 5.39 | Oct 11

Immune Regulation News 5.39 October 11, 2013
Pulmonary Cell News
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Cyclic Dinucleotides Trigger ULK1 (ATG1) Phosphorylation of STING to Prevent Sustained Innate Immune Signaling
The authors demonstrated that, after autophagy-dependent stimulator of interferon genes (STING) delivery of TANK-binding kinase 1 to endosomal/lysosomal compartments and activation of transcription factors interferon regulatory factor 3 (IRF3) and NF-κB, STING is subsequently phosphorylated by serine/threonine UNC-51-like kinase (ULK1), and IRF3 function is suppressed. ULK1 activation occurred following disassociation from its repressor AMP activated protein kinase and was elicited by cyclic dinucleotides generated by the cGAMP synthase, cGAS. [Cell] Abstract | Graphical Abstract
Free Nature Reviews Immunology Poster: The Immune Response to HIV
PUBLICATIONS (Ranked by impact factor of the journal)
Steady-State Production of IL-4 Modulates Immunity in Mouse Strains and Is Determined by Lineage Diversity of iNKT Cells
Invariant natural killer T cells (iNKT cells) can produce copious amounts of interleukin 4 (IL-4) early during infection. However, indirect evidence suggests they may produce this immunomodulatory cytokine in the steady state. Through intracellular staining for transcription factors, the authors have defined three subsets of iNKT cells that produced distinct cytokines; these represented diverse lineages and not developmental stages, as previously thought. [Nat Immunol] Abstract

Epigenetic Modifications Induced by Blimp-1 Regulate CD8+ T Cell Memory Progression during Acute Virus Infection
Scientists found that increased proliferation and survival of Blimp-1-deficient CD8+ T cells resulted from sustained expression of CD25 and CD27 and persistent cytokine responsiveness. Silencing of Il2ra and Cd27 reduced the Blimp-1-deficient CD8+ T cell response. [Immunity] Abstract

A Single Peptide-Major Histocompatibility Complex Ligand Triggers Digital Cytokine Secretion in CD4+ T Cells
Investigators found that naive T cells, T cell blasts, and memory T cells could all be triggered by a single peptide-major histocompatibility complex (pMHC) to secrete tumor necrosis factor-α and interleukin-2 cytokines with a rate of 1,000, 10,000, and 10,000 molecules/min, respectively, and that additional pMHCs did not augment secretion, indicating a digital response pattern. [Immunity] Abstract

Granzyme B Degradation by Autophagy Decreases Tumor Cell Susceptibility to Natural Killer-Mediated Lysis Under Hypoxia
Researchers demonstrated that hypoxia impairs breast cancer cell susceptibility to natural killer (NK)-mediated lysis in vitro via the activation of autophagy. This impairment was not related to a defect in target cell recognition by NK cells but to the degradation of NK-derived granzyme B in autophagosomes of hypoxic cells. [Proc Natl Acad Sci USA] Abstract

The TNF Family Member 4-1BBL Sustains Inflammation by Interacting with TLR Signaling Components During Late-Phase Activation
Toll-like receptor 4 (TLR4)-mediated inflammation, which occurs in two phases, depends on the TNF family member 4-1BB ligand (4-1BBL) to sustain tumor necrosis factor-α (TNF-α) production during late-phase signaling. Scientists showed that Toll-interleukin-1 receptor domain-containing adaptor protein and the kinase IRAK2 interacted with 4-1BBL to mediate late-phase TLR4 signaling. [Sci Signal]
| Press Release

IVIg Immune Reconstitution Treatment Alleviates the State of Persistent Immune Activation and Suppressed CD4 T Cell Counts in CVID
Researchers addressed the hypothesis that poor antibody-mediated immune control of infections may result in substantial perturbations in the T cell compartment. Newly diagnosed common variable immunodeficiency (CVID) patients were sampled before, and 6-12 months after, initiation of intravenous immunoglobulin (IVIg) therapy. [PLoS One] Full Article

Serotonin 5-HT2A Receptor Activation Blocks TNF-α Mediated Inflammation In Vivo
Recently, the authors discovered that selective activation of serotonin 5-HT2A receptors with the agonist (R)-DOI produces a super-potent blockade of proinflammatory markers in primary rat aortic smooth muscle cells. Here, they demonstrated that systemic administration of (R)-DOI can block the systemic effects of tumor necrosis factor alpha (TNF-α) in whole animal, with potent anti-inflammatory effects in the aortic arch and small intestine. [PLoS One] Full Article | Press Release

Bisphosphonates Target B Cells to Enhance Humoral Immune Responses
Investigators showed that the administration of clinically relevant doses of bisphosphonates in mice increases antibody responses to live and inactive viruses, proteins, haptens, and existing commercial vaccine formulations. Bisphosphonates target directly B cells and enhance B cell expansion and antibody production upon antigen encounter. [Cell Rep] Full Article | Graphical Abstract

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A New System for High-Throughput Cell Isolation Directly from Whole Blood
Immune Regulation by Atypical Chemokine Receptors
The authors discuss the biochemical and immunological properties of atypical chemokine receptors and the potential unifying themes in this family, and they highlight recent studies that identify novel roles for these molecules in development, homeostasis, inflammatory disease, infection and cancer. [Nat Rev Immunol] Abstract

Fueling Immunity: Insights into Metabolism and Lymphocyte Function
This review highlights emerging concepts regarding metabolic reprogramming in proliferating cells and discuss their potential impact on T cell fate and function. [Science] Abstract

Role of Type 1 Natural Killer T Cells in Pulmonary Immunity
The authors review the dual role of mucosal natural killer T (NKT) cells during immune responses and pathologies with a particular focus on the lungs. Their role during pulmonary acute and chronic inflammation and respiratory infections is outlined. [Mucosal Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation field.
Clinical Trial Harnesses Power of Natural Killer Cells to Treat Neuroblastoma
Solving Kids’ Cancer and The Catherine Elizabeth Blair Memorial Foundation awarded a $136,000 grant to support the novel immunotherapy clinical trial for childhood cancer. [Solving Kids’ Cancer] Press Release

Tapimmune Announces Development of Advanced Immunotherapeutic Vaccine Expression and Delivery System
TapImmune announced development of an immunotherapeutic vaccine expression and delivery system. The novel platform is termed TapImmune’s PolyStart™ technology and has been strategically designed to directly enhance the immune system’s ability to stimulate either or BOTH cytotoxic killer and helper T-cell reactive proprietary peptides, known and expected to be associated with one, or more importantly, ANY cancer, infectious disease or bio-threat. [TapImmune Inc.] Press Release

OncoSec Medical Announces Positive Preliminary Safety Data in Combination Study
OncoSec Medical Inc. has announced positive preliminary animal data demonstrating the benefits of combining the company’s ImmunoPulse with anti-CTLA4 and anti-PD1 antibodies. [OncoSec Medical Inc.] Press Release

Roswell Park Cancer Institute, University of Pittsburgh Cancer Institute Awarded $11 Million SPORE Grant
With more than $11 million in funding from the National Cancer Institute, Roswell Park Cancer Institute, in collaboration with the University of Pittsburgh Cancer Institute, will embark on a search for ways to prevent and cure ovarian cancer. Distributed over five years, the funds will come through a Specialized Program of Research Excellence (SPORE) grant. The research team will study novel immunotherapy approaches for the treatment of and risk assessment for ovarian cancer. [Roswell Park Cancer Institute] Press Release

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NEW Spring 2014 Meeting of the Canadian Society for Immunology (CSI)
March 6-9, 2014
Quebec City, Canada

NEW 9th International Congress on Autoimmunity
March 26-30, 2014
Nice, France

Visit our events page to see a complete list of events in the immune regulation community.
NEW Postdoctoral Fellow – Anti-Tumor Immunity (H. Lee Moffitt Cancer Center & Research Institute)

NEW Postdoctoral Research Fellow – Immunotherapy (Washington University School of Medicine)

Senior Principal Scientist – Immunology (Johnson & Johnson)

Postdoctoral Fellow – Ripk1 in Innate Immune Responses and Necroptosis (University of Massachusetts Medical School)

PhD Position – T-Lymphocyte Antigen Recognition (Medical University of Vienna)

Research Fellow – Immunology (Queen’s University Belfast)

PhD/Postdoctoral Positions – Quantitative T-Cell Immunology (University of Leeds)

Postdoctoral Fellowship – Immunology (Johns Hopkins University School of Medicine)

PhD Research Position – Molecular and Cellular Mechanisms of Immune Tolerance and Autoimmunity (Weizmann Institute of Science)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Technologist – Cell Culture Media & Matrices (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

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