Immune Regulation News Volume 6.43 | Nov 14 2014

mTOR Kinase Inhibitors Promote Antibody Class Switching via mTORC2 Inhibition
The authors show that high concentrations of ATP-competitive mammalian target of rapamycin (mTOR) kinase inhibitors suppress B-cell proliferation and differentiation, yet lower concentrations that preserve proliferation increase the fraction of B cells undergoing class switching in vitro. [Proc Natl Acad Sci USA] Abstract

A Novel Mechanism of B Cell-Mediated Immune Suppression through CD73 Expression and Adenosine Production
Investigators identified a novel population of B cells that expresses CD73 as well as CD39, two ectoenzymes that together catalyze the extracellular dephosphorylation of adenine nucleotides to adenosine. [J Immunol] Abstract

Infiltrating Regulatory B Cells Control Neuroinflammation following Viral Brain Infection
In vivo and in vitro experiments were undertaken to elucidate the role of regulatory B cells in controlling neuroinflammation following viral brain infection. Scientists used multicolor flow cytometry to phenotype lymphocyte subpopulations infiltrating the brain, along with in vitro cocultures to assess their anti-inflammatory and immunoregulatory roles. [J Immunol] Abstract

IFN-γ Induces Aberrant CD49b⁺ NK Cell Recruitment through Regulating CX3CL1: A Novel Mechanism by which IFN-γ Provokes Pregnancy Failure
Findings indicate that interferon-γ (IFN-γ) can significantly increase uterine CX3CL1 expression via activation of the Janus family kinase 2-signal transducers and activators of transcription 1 pathway, thus inducing CD49b⁺ natural killer (NK) cell uterine homing, and eventually provoke fetal loss. [Cell Death Dis] Full Article

PGRN Protects against Colitis Progression in Mice in an IL-10 and TNFR2 Dependent Manner
Investigators sought to determine the role and regulation of progranulin (PGRN) in the pathogenesis of inflammatory bowel diseases. Hematopoietic-derived PGRN was critical for protection against dextran sulfate sodium-induced colitis, and lack of PGRN signaling in CD4⁺ T cells also exacerbated experimental colitis. [Sci Rep] Full Article

Immature Dendritic Cells Convert Anergic Non-Regulatory T Cells into Foxp3^– IL-10⁺ Regulatory T Cells by Engaging CD28 and CTLA-4
Researchers induced peptide-specific anergy in T cells from mice by co-culturing anergic T cells with immature murine dendritic cells (DCs). They found that these anergic, non-suppressive IL-10^– Foxp3^– CTLA-4⁺ CD25^low Egr2⁺ T cells, could be converted into suppressive IL-10⁺ Foxp3^– CTLA-4⁺ CD25^high Egr2⁺ cells resembling type-1 regulatory T cells when stimulated a second time by immature DCs in vitro. [Eur J Immunol] Abstract

CD3^bright Signals on γδ T Cells Identify IL-17A-Producing Vγ6Vδ1⁺ T Cells
γδ T cells are recognized as interleukin-17 (IL-17) producers, but based on the level of CD3 expression, researchers now define the remarkable ability of a CD3^bright γδ T-cell subset with an effector memory phenotype to rapidly produce IL-17A, but not interferon-γ. [Immunol Cell Biol] Abstract

BDC12-4.1 T-Cell Receptor Transgenic Insulin-Specific CD4 T Cells Are Resistant to In Vitro Differentiation into Functional Foxp3⁺ T Regulatory Cells
As insulin is the major autoantigen leading to type 1 diabetes, scientists tested the capacity of insulin-specific T-cell receptor transgenic CD4⁺ T cells of the BDC12-4.1 clone to convert into Foxp3⁺ induced T regulatory cells. [PLoS One] Full Article

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Innovimmune to Present Superior Preclinical Therapeutic Efficacy Results in Rheumatoid Arthritis of Its INV-17 RORγt Inhibitor Program
Innovimmune Biotherapeutics Holding, LLC will present data demonstrating successful treatment of rheumatoid arthritis in a murine collagen-induced arthritis model with its proprietary oral small molecule retinoic acid receptor-related orphan receptor gamma t (RORγt) modulators from their INV-17 portfolio. [Press release from Innovimmune Biotherapeutics Holding, LLC (GlobeNewswire Inc.) discussing research to be presented at the 2014 American College of Rheumatology (ACR) Annual Meeting, Boston] Press Release

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Stellar Biotechnologies and Araclon Biotech Sign Exclusive KLH Supply Agreement for Clinical Trials in Alzheimer’s Active Immunotherapies
Stellar Biotechnologies, Inc. and Araclon Biotech SL announced that the companies have executed a definitive exclusive supply agreement to meet Araclon’s Phase II/III clinical trial requirements for Keyhole Limpet Hemocyanin (KLH) used in Araclon’s active immunotherapies against Alzheimer’s disease. [Stellar Biotechnologies, Inc.] Press Release

Advaxis Submits Investigational New Drug Application for Phase I/II Study of ADXS-HPV and MedImmune’s MEDI4736 for the Treatment of HPV-Associated Cervical and Head & Neck Cancer
Advaxis, Inc. announced that the Company has submitted an Investigational New Drug application to the United States Food and Drug Administration to conduct a Phase I/II study of ADXS-HPV alone or in combination with MedImmune’s investigational anti-PD-L1 immune checkpoint inhibitor, MEDI4736, for the treatment of advanced, recurrent or refractory human papillomavirus (HPV)-associated cervical cancer and HPV-associated head and neck cancer. [Advaxis, Inc.] Press Release

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NEW 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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