Immune Regulation News Volume 6.44 | Nov 21 2014

The Angiogenic Factor PlGF Mediates a Neuroimmune Interaction in the Spleen to Allow the Onset of Hypertension
Researchers show a splenic role for placental growth factor (PlGF), which accounts for the onset of hypertension, through immune system modulation. PlGF repressed the expression of the protein Timp3 (tissue inhibitor of metalloproteinases 3), which allowed costimulation of T cells and their deployment toward classical organs involved in hypertension. [Immunity] Abstract | Graphical Abstract | Editorial

CXCR4 and a Cell-Extrinsic Mechanism Control Immature B Lymphocyte Egress from Bone Marrow
Investigators used two-photon intravital microscopy to show that immature B cell retention within bone marrow (BM) was strictly dependent on amoeboid motility mediated by CXCR4 and CXCL12 and by α4β1 integrin-mediated adhesion to VCAM-1. Immature B cell egress from BM was dependent on a twofold CXCR4 down-regulation that was antagonized by antigen-induced BCR signaling. [J Exp Med] Abstract | Editorial

Optimal T-Cell Receptor Affinity for Inducing Autoimmunity
Three transgenic mouse strains expressing antigens of variable affinity for the OVA transgenic-I T-cell receptor were generated to address how TCR affinity affects the efficiency of negative selection, the ability to prime an autoimmune response, and the elimination of the relevant target cell. Mice expressing antigens with an affinity just above the negative selection threshold exhibited the highest risk of developing experimental autoimmune diabetes. [Proc Natl Acad Sci USA] Abstract

Uncoupling Malt1 Threshold Function from Paracaspase Activity Results in Destructive Autoimmune Inflammation
Researchers demonstrate that targeted Malt1-paracaspase inactivation induces a lethal inflammatory syndrome with lymphocyte-dependent neurodegeneration in vivo. In addition to NF-κB inhibitors, Malt1 cleaves an entire set of mRNA stability regulators and paracaspase inactivation results in excessive interferon gamma production by effector lymphocytes that drive pathology. [Cell Rep] Full Article | Graphical Abstract | Press Release

Docosahexaenoic Acid Alleviates Atopic Dermatitis by Generating Treg and IL-10/TGF-β-Modified Macrophage via TGF-β Dependent Mechanism
Investigators examined whether docosahexaenoic acid (DHA) suppresses allergic reactions and up-regulates the generation of CD4⁺Foxp3⁺ T cells. They also examined the effects of transfusing IL-10/TGF-β-modified macrophages treated with DHA into a mouse model of atopic dermatitis. [J Invest Dermatol] Abstract

Mice Lacking Axl and Mer Tyrosine Kinase Receptors Are Susceptible to Experimental Autoimmune Orchitis Induction
Investigators aimed to determine the role of Axl and Mer receptor tyrosine kinases in maintaining the systemic tolerance to male germ cell antigens using the experimental autoimmune orchitis model. [Immunol Cell Biol] Abstract

A Pneumocyte-Macrophage Paracrine Lipid Axis Drives the Lung Toward Fibrosis
Scientists demonstrate that oxidized phospholipids accumulate within alveolar macrophages (AM) after bleomycin injury, and that murine and human AMs treated with oxidized phosphatidylcholine become polarized along an M2 phenotype and display enhanced production of TGF-β1. [Am J Respir Cell Mol Biol]
Abstract | Press Release

Novel and Enhanced Anti-Melanoma DNA Vaccine Targeting the Tyrosinase Protein Inhibits Myeloid-Derived Suppressor Cells and Tumor Growth in a Syngeneic Prophylactic and Therapeutic Murine Model
Scientists investigated the role of myeloid-derived suppressor cells in immune suppression of T cells in an antigen-specific B16 melanoma murine system utilizing a novel synthetic tyrosinase DNA vaccine therapy in both prophylactic and therapeutic models. [Cancer Gene Ther] Abstract | Press Release

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Kineta Presents Encouraging Safety and Efficacy Data for Lead Autoimmune Drug ShK-186
Kineta, Inc. announced updated results from its Phase I clinical trials showing ShK-186 well tolerated with no moderate or serious adverse events reported and potential effectiveness in additional autoimmune diseases. [Press release from Kineta, Inc. discussing research at the American College of Rheumatology (ACR) Annual Meeting, Boston] Press Release | Poster

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UB Researchers Awarded Patent for Sjögren’s Syndrome Test
Researchers from the University at Buffalo have been awarded a patent for a test that allows physicians to diagnose the autoimmune disease Sjögren’s syndrome earlier than ever before. [University at Buffalo] Press Release

SOTIO Initiates US Part of VIABLE, a Global Phase III Clinical Trial for Prostate Cancer Immunotherapy Treatment Using DCVAC/PCa
SOTIO announced that the first US patient has been enrolled in its VIABLE study, the global Phase III clinical trial for DCVAC/PCa, an active cellular immunotherapy treatment for prostate cancer patients. Initial patients were also recently enrolled into the study in Italy, UK, the Netherlands and Slovakia. [SOTIO, LLC] Press Release

Kite Pharma Receives Positive Opinion for Orphan Drug Designation in the European Union for KTE-C19, Kite’s Lead Investigational Cancer Immunotherapy
Kite Pharma, Inc., announced that the European Medicines Agency Committee for Orphan Medicinal Products has adopted a positive opinion recommending KTE-C19 for designation as an orphan medicinal product for the treatment of diffuse large B cell lymphoma. [Kite Pharma, Inc.] Press Release

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NEW Researcher – Antitumor Immune Cell Response (ACAVI)

Research Technician – Cancer and Inflammatory Diseases (Qu Biologics Inc.)

Research Scientist – Cancer and Inflammatory Diseases (Qu Biologics Inc.)

Postdoctoral Scientist – Immunotherapy (Children’s Hospital of Eastern Ontario Research Institute)

Head of Cellular and Molecular Therapies Laboratory (NHS Blood & Transplant)

Postdoctoral Research Fellow – Immune and Pathogenic Mechanisms during Alphavirus Infection (Singapore Immunology Network A*STAR)

Postdoctoral Research Fellow – Immune Responses to HSV (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Genetic and Epigenetic Regulatory Networks in Protective Immune Responses (Washington University School of Medicine)

PhD Studentship – Cancer Immunology (Cardiff University)

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

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