Immune Regulation News Volume 6.13 | Apr 11 2014

Protein Kinase C-η Controls CTLA-4-Mediated Regulatory T Cell Function
Regulatory T (Treg) cells form an immunological synapse (IS) with antigen-presenting cells. However, signaling events at the Treg cell IS remain unknown. Researchers showed that the kinase PKC-η associated with CTLA-4 and was recruited to the Treg cell IS. [Nat Immunol] Abstract | Press Release

EAT-2, a SAP-Like Adaptor, Controls NK Cell Activation through Phospholipase Cγ, Ca⁺⁺, and Erk, Leading to Granule Polarization
Investigators used a variety of genetic, biochemical, and imaging approaches to define the molecular and cellular mechanisms by which Ewing’s sarcoma-associated transcript 2 (EAT-2) controls natural killer (NK) cell activation. [J Exp Med] Abstract | Press Release

CXCL11-Dependent Induction of FOXP3-Negative Regulatory T Cells Suppresses Autoimmune Encephalomyelitis
Researchers showed that CXCL10/CXCR3 interactions drive effector Th1 polarization via STAT1, STAT4, and STAT5 phosphorylation, while CXCL11/CXCR3 binding induces an immunotolerizing state that is characterized by IL-10^hi and IL-4^hi cells, mediated via p70 kinase/mTOR in STAT3- and STAT6-dependent pathways. [J Clin Invest] Full Article

The Phosphatase JKAP/DUSP22 Inhibits T-Cell Receptor Signaling and Autoimmunity by Inactivating Lck
The in vivo role of JNK pathway-associated phosphatase (JKAP, also known as DUSP22) in immune regulation remains unclear. Researchers report that JKAP directly inactivates Lck by dephosphorylating tyrosine-394 residue during T-cell receptor signaling. JKAP-knockout T cells display enhanced cell proliferation and cytokine production. [Nat Commun] Abstract

Inverse Hormesis of Cancer Growth Mediated by Narrow Ranges of Tumor-Directed Antibodies
It remains generally unclear whether the immune responses that mediate cancer immunosurveillance vs. those responsible for inflammatory facilitation are qualitatively and/or quantitatively distinct. Researchers addressed this question using multiple murine tumor growth models in which polyclonal antibodies against tumor antigens, such as N-glycolyl-neuraminic acid, can alter tumor progression. [Proc Natl Acad Sci USA]
Abstract | Press Release

Regeneration of the Aged Thymus by a Single Transcription Factor
Scientists showed that forced, thymic epithelial cell-specific upregulation of Forkhead box N1 in the fully involuted thymus of aged mice results in robust thymus regeneration characterized by increased thymopoiesis and increased naive T cell output. [Development] Full Article | Press Release

Wnt5a-Rac1-NF-κB Homeostatic Circuitry Sustains Innate Immune Functions in Macrophages
Wnt5a-Fz5 signaling being a primordial event during cell differentiation, scientists examined the involvement of Wnt5a-Fz5 signaling in the maintenance of innate immune functions. They demonstrated that innate immune functions of macrophages ensue at least partly through a homeostatic Wnt5a-Fz5-NF-κB (p65) circuit, which is Rac1 dependent. [J Immunol] Abstract

Homeobox Transcription Factor VentX Regulates Differentiation and Maturation of Human Dendritic Cells
Researchers report that ablation of VentX expression in monocytes significantly impaired their differentiation into dendritic cells (DCs). Conversely, overexpression of VentX in monocytic THP1 cells accelerated their differentiation towards DCs. The authors showed that VentX regulates DC differentiation, in part, through modulating IL6 expression. [J Biol Chem] Abstract | Full Article

Mast Cell-Derived Serine Proteinase Regulates T Helper 2 Polarization
The authors investigated the role of mast cells in immune regulation during aberrant T helper 2 responses. [Sci Rep] Full Article

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Immune Responses Enhanced and Sustained when PROVENGE^® (Sipuleucel-T) Is Given after Androgen Deprivation Therapy in Biochemically-Recurrent Prostate Cancer
Dendreon Corporation announced preliminary data from a long-term analysis of the Phase II STAND study demonstrating that tumor-specific T-cell responses appear to be enhanced and sustained when PROVENGE^® (sipuleucel-T) is given after androgen deprivation therapy in patients with biochemically-recurrent prostate cancer at high risk for metastases. [Press release from Dendreon Corporation discussing research presented at the 29^th Annual European Association of Urology (EAU) Congress, Stockholm] Press Release

Disruption of VISTA Plays an Important Role in Regulating Immune Response
Researchers have found that the body’s immune system response was enhanced when they disrupted VISTA, a protein that prevents the immune system from overreacting. [Press release from the Norris Cotton Cancer Center discussing research presented at the American Association for Cancer Research (AACR) Annual Meeting 2014, San Diego] Press Release

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Regeneus Partners with US Specialist Manufacturer for Its Canine Cancer Immunotherapy
Regeneus announced that it has partnered with US specialist veterinary vaccine manufacturer, Hennessy Research, for the production of Regeneus’ new autologous canine cancer immunotherapy, Kvax. [Regeneus Ltd] Press Release

Oncothyreon Announces Merck KGaA, Darmstadt, Germany, Initiation of Phase III START2 Study with Tecemotide in Stage III Non-Small Cell Lung Cancer
Oncothyreon Inc. announced that Merck KGaA, Darmstadt, Germany, has initiated the international Phase III START2 study, which is designed to assess the efficacy and safety of the investigational MUC1 antigen-specific cancer immunotherapy tecemotide (also known as L-BLP25) in patients with unresectable, locally advanced Stage III non-small cell lung cancer. [Oncothyreon Inc.] Press Release

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NEW Postdoctoral Position – Neuro-Immune Interactions (ICM Foundation – Brain and Spinal Cord Research Institute)

NEW Postdoctoral Research Associate – Infection and Immunity (University College London)

Postdoctoral Associate – Immunology (Virginia Bioinformatics Institute at Virginia Tech)

Postdoctoral Position – Immunology (University of Pittsburgh)

Director of GMP/GLP Quality Operations (University of Pennsylvania, Perelman School of Medicine)

Postdoctoral Research Scientist – Molecular Mechanisms of Leukemia Immune Evasion (San Raffaele Scientific Institute)

PhD Student – Immunometabolic Networks Regulating the Innate Immune Response (Radboud University Medical Center)

Research Group Leader – Basic Mechanisms and Regulation of Inflammation (University Medical Center Hamburg-Eppendorf)

Professor – Cancer Research (Yale University School of Medicine)

Assistant/Associate Professors – Allergic Inflammation and Sensory Neurobiology (North Carolina State University College of Veterinary Medicine)

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

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

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