Immune Regulation News Volume 7.39 | Oct 16 2015

IL-17A Is Increased in Humans with Primary Hyperparathyroidism and Mediates PTH-Induced Bone Loss in Mice
Investigators showed that the inflammatory cytokine IL-17A is upregulated by primary hyperparathyroidism in humans and continuous PTH (cPTH) in mice. Mechanistically, cPTH stimulates conventional T cell production of TNFα, which increases the differentiation of IL-17A-producing Th17 cells via TNF receptor 1 signaling in CD4⁺ cells. [Cell Metab] Abstract | Graphical Abstract | Press Release

Blood Coagulation Protein Fibrinogen Promotes Autoimmunity and Demyelination via Chemokine Release and Antigen Presentation
Researchers showed that fibrinogen, a central blood coagulation protein deposited in the central nervous system (CNS) after blood–brain barrier disruption, induces encephalitogenic adaptive immune responses and peripheral macrophage recruitment into the CNS leading to demyelination. [Nat Commun] Full Article | Press Release

Treg17 Cells Are Programmed by Stat3 to Suppress Th17 Responses in Systemic Lupus
Although Th17 cells are thought to be central mediators of systemic lupus erythematosus, mechanisms underlying their counter regulation remain largely unknown. To help define this, scientists studied the function of the newly defined Stat3-dependent Th17-specific regulatory T cells (Treg17). [Kidney Int] Abstract

Pathways Responsible for Human Autoantibody and Therapeutic Intravenous IgG Activity in Humanized Mice
Investigators showed that the human immunoglobulin G (IgG) subclass strongly impacts autoantibody activity and that the Fc-receptor genotype of the human donor immune system further modulates autoantibody activity. Human mononuclear phagocytes were responsible for autoantibody activity, and intravenous IgG therapy was able to suppress disease pathology in an Fc-fragment-dependent manner. [Cell Rep]
Full Article | Graphical Abstract

The Timing of Stimulation and IL-2 Signaling Regulate Secondary CD8 T Cell Responses
Scientists addressed the mechanisms involved in the generation and development of secondary (2°) memory (M) CD8 T cells. They observed that the time at which primary M CD8 T cells enter into immune response impacts their fate and differentiation into 2° M CD8 T cells. [PLoS Pathog] Full Article

MyD88 in Donor Bone Marrow Cells Is Critical for Protection from Acute Intestinal Graft-vs.-Host Disease
To understand the role of myeloid differentiation factor 88 (MyD88) expressed by donor bone marrow (BM) in the pathophysiology of graft-vs.-host disease (GvHD), researchers investigated the effects of transplantation of MyD88-deficient T cell-depleted BM on the severity of GvHD. [Mucosal Immunol] Abstract

TAK1 Inhibition Prevents the Development of Autoimmune Diabetes in NOD Mice
Investigators postulated that blockade of transforming growth factor-β activated kinase-1 (TAK1) would affect autoimmune diabetes in non-obese diabetic (NOD) mice. TAK1 inhibition by 5Z-7-oxozeaenol elicited a Th1 to Th2 cytokine shift, and increased TGF-β1 production in cultured T lymphocytes supernatants. [Sci Rep] Full Article

Effective Intrahepatic CD8⁺ T-Cell Immune Responses Are Induced by Low but Not High Numbers of Antigen-Expressing Hepatocytes
Scientists aimed at elucidating the impact of different intrahepatic antigen loads on the quality of CD8⁺ T-cell-mediated immunity by employing an infection-free transgenic mouse model expressing ovalbumin (Ova) as the target antigen. Adoptive transfer of OT-I cells induced a transient intrahepatic immune response toward both high and low Ova levels. [Cell Mol Immunol] Full Article

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Sizing up the Key Determinants of the CD8⁺ T Cell Response
Recent technological advances have allowed scientists to more accurately identify, characterize and quantitate key determinants that define the specificity and magnitude of CD8⁺ T cell-mediated immunity. The authors discuss the technical and conceptual advances that have markedly changed the understanding of the determinants of primary cytotoxic T lymphocyte responses. [Nat Rev Immunol] Abstract

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AstraZeneca and Peregrine Pharmaceuticals Expand Ongoing Immuno-Oncology Collaboration to Include Phase II Lung Cancer Combination Clinical Trial
Peregrine Pharmaceuticals, Inc. announced that it has expanded its ongoing cancer immunotherapy clinical collaboration with AstraZeneca to include a second, later-stage trial. [Peregrine Pharmaceuticals, Inc.] Press Release

Celsion Announces Impressive Preclinical Data for Its GEN-1 IL-12 Immunotherapy in Combination with Avastin^® and Doxil^® for Ovarian Cancer
Results from the comprehensive studies confirmed remarkable initial GEN-1 + Avastin^® findings and show convincingly that GEN-1 when combined with Avastin^® and Doxil^®, standard of care for platinum resistant patients, demonstrated a greater than 98% reduction in tumor burden when compared to the untreated control group. [Celsion Corporation] Press Release

OncoQR’s Breast Cancer Vaccine Successfully Completes Pre-Clinical Proof-of-Concept Study
OncoQR ML announced that its breast cancer vaccine candidate OQR200 has successfully completed a proof-of-concept study in non-human primates. The vaccine elicited the expression of very high levels of polyclonal antibodies targeting multiple epitopes on Her2/neu. [OncoQR ML (B3C Group GmbH)] Press Release

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NEW Postdoctoral Fellow – Immunology (Klinikum Rechts der Isar Technische Universitat Munchen)

NEW Research Scientist – Tumor Immunology (iTeos Therapeutics)

Project Manager – Manufacturing (Qu Biologics)

Postdoctoral Research Fellow/Research Scientist – Biotechnology (Qu Biologics)

Postdoctoral Fellow – Cancer Biology (The University of Texas MD Anderson Cancer Center)

Professor – Immunology (La Jolla Institute for Allergy & Immunology)

Canadian Research Chair Tier 1 – Systems Immunology (University of Manitoba)

Scientist Position – Role of Inflammation and the Immune System in the Context of Tissue Regeneration (KU Leuven)

Postdoctoral Position – Immunology (Shanghai Institute of Immunology)

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