Immune Regulation News Volume 6.46 | Dec 5 2014

A p85α-Osteopontin Axis Couples the Receptor ICOS to Sustained Bcl-6 Expression by Follicular Helper and Regulatory T Cells
Investigators report that activation of ICOS in CD4⁺ T cells promoted interaction of the p85α regulatory subunit of the signaling kinase PI3K and intracellular osteopontin (OPN-i), followed by translocation of OPN-i to the nucleus, its interaction with Bcl-6 and protection of Bcl-6 from ubiquitin-dependent proteasome degradation. [Nat Immunol] Abstract

The Immunoreceptor TIGIT Regulates Antitumor and Antiviral CD8⁺ T Cell Effector Function
TIGIT is highly expressed on human and murine tumor-infiltrating T cells, and, in models of both cancer and chronic viral infection, antibody coblockade of TIGIT and PD-L1 synergistically and specifically enhanced CD8⁺ T cell effector function, resulting in significant tumor and viral clearance, respectively. [Cancer Cell]
Abstract | Graphical Abstract

Multiple Functional Therapeutic Effects of the Estrogen Receptor β Agonist Indazole-Cl in a Mouse Model of Multiple Sclerosis
Therapeutic indazole chloride improved clinical disease and rotorod performance and also decreased peripheral Th1 cytokines and reactive astrocytes, activated microglia, and T cells in brains of experimental autoimmune encephalomyelitis mice. [Proc Natl Acad Sci USA] Abstract | Full Article | Press Release

Activation of Toll-Like Receptor-2 by Endogenous Matrix Metalloproteinase-2 Modulates Dendritic-Cell-Mediated Inflammatory Responses
Investigators show that matrix metalloproteinase-2 (MMP-2) directly stimulates dendritic cells to both upregulate OX40L on the cell surface and secrete inflammatory cytokines. MMP-2 polarizes T cells toward type 2 responses in vivo, in a Toll-like receptor-2-dependent manner. [Cell Rep]
Full Article | Graphical Abstract | Press Release

Regulatory T Cells Occupy an Isolated Niche in the Intestine that Is Antigen Independent
Regulatory T cells (Tregs) require antigen-specific signals via T cell receptor-major histocompatibility complex class II (TCR-MHCII) interactions for their development. Scientists examined lamina propria Treg homeostasis in a transgenic mouse model that lacks peripheral TCR-MHCII interactions and generation of extrathymic Tregs. [Cell Rep] Full Article | Graphical Abstract

Splenic B Cells from Hymenolepis diminuta-Infected Mice Ameliorate Colitis Independent of T Cells and via Cooperation with Macrophages
In response to H. diminuta, a putatively unique splenic CD19⁺ B cell with a functional immunoregulatory program is generated that promotes the suppression of colitis dominated by TH1, TH2, or TH1-plus-TH2 events, and may do so via the synthesis of TGF-β and the generation of, or cooperation with, a regulatory macrophage. [J Immunol] Abstract

Natural Killer T Cells Play a Necessary Role in Modulating of Immune-Mediated Liver Injury by Gut Microbiota
Oral administration of pathogenic bacteria or gentamycin to mice before ConA injection, liver injury and lymphocyte distribution in liver and intestine were assessed. Activation-induced natural killer T cells were downregulated in the liver of pathogenic bacteria-treated ConA groups. [Sci Rep] Full Article

DNA Vaccination Strategy Targets Epidermal Dendritic Cells, Initiating Their Migration and Induction of a Host Immune Response
Scientists demonstrate that intradermally electroporation-enhanced pDNA vaccination results in the rapid induction of a host humoral immune response. Furthermore, they delineate the relationship between the migration of directly transfected epidermal dendritic cells and the generation of the host immune response. [Mol Ther Methods Clin Dev] Full Article

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ZIOPHARM and Intrexon Present Clinical and Preclinical Data
ZIOPHARM Oncology, Inc. and Intrexon Corporation announced the presentation of clinical and preclinical studies from their immuno-oncology programs. [Press release from ZIOPHARM Oncology, Inc. discussing research presented at the American Association for Cancer Research (AACR) 2014 Immunology and Immunotherapy Meeting, Orlando] Press Release

Idera Pharmaceuticals Announces Cancer Immunotherapy Regimen with Intratumoral IMO-2055 Demonstrated Potent and Systemic Anti-Tumor Activity in Preclinical Models
Idera Pharmaceuticals, Inc. announced new preclinical data that showed cancer immunotherapy with intratumoral injections of IMO-2055 and ipilimumab demonstrated potent and systemic anti-tumor activity in multiple preclinical cancer models. [Press release from Idera Pharmaceuticals, Inc. discussing research presented at the American Association for Cancer Research (AACR) 2014 Immunology and Immunotherapy Meeting, Orlando] Press Release

Genentech to Present Clinical Data from Six Different Medicines
Genentech announced that new data on four investigational medicines and investigational uses for two approved hematology medicines will be presented. [Press release from Genentech, Inc. discussing research to be presented at the 56^th American Society of Hematology (ASH) Annual Meeting, San Francisco] Press Release

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TxCell Announces Start of Phase IIb Clinical Trial with Ovasave^® for Refractory Crohn’s Disease
TxCell SA announced that it has enrolled the first patient in its Phase IIb clinical trial of its lead product Ovasave^® in refractory Crohn’s disease. [TxCell SA] Press Release

MRIGlobal Wins Contract to Produce HPV Vaccine
MRIGlobal announced that it has been awarded a $3 million contract amendment from the National Cancer Institute’s PREVENT Cancer Program to provide a vaccine for the Human Papillomavirus or HPV. MRIGlobal will lead a team that will produce the vaccine to be used in a Phase I clinical trial. [MRIGlobal] Press Release

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NEW Postdoctoral Position – Immunology (Centre Léon Bérard)

Postdoctoral Position – Mucosal Immunology (Karolinska Institute)

Research Associate – B Cell Biology (King’s College London)

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PhD Studentship – Cancer Immunology (Cardiff University)

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

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

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