Volume 5.36 | Sep 20

Immune Regulation News 5.36 September 20, 2013
Pulmonary Cell News
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Human SNP Links Differential Outcomes in Inflammatory and Infectious Disease to a FOXO3-Regulated Pathway
Investigators identified a noncoding polymorphism in FOXO3A at which the minor allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn’s disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFβ1 reduces production of proinflammatory cytokines, including TNFα, and increases production of anti-inflammatory cytokines, including IL-10. [Cell] Abstract | Graphical Abstract | Full Article
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PUBLICATIONS (Ranked by impact factor of the journal)
Intestinal Monocytes and Macrophages Are Required for T Cell Polarization in Response to Citrobacter rodentium
Scientists describe a two-gene approach that requires overlapping expression of LysM and Csf1r to define and deplete monocytes and macrophages. The role of monocytes and macrophages in immunity to pathogens was tested by their selective depletion during infection with Citrobacter rodentium. [J Exp Med] Abstract

Inhibiting Glycolytic Metabolism Enhances CD8+ T Cell Memory and Antitumor Function
The authors used a fluorescent glucose analog, 2-NBDG, to quantify glucose uptake in activated CD8+ T cells. They found that cells exhibiting limited glucose incorporation had a molecular profile characteristic of memory precursor cells and an increased capacity to enter the memory pool compared with cells taking up high amounts of glucose. [J Clin Invest] Full Article | Press Release

Targeted Delivery of Proapoptotic Peptides to Tumor-Associated Macrophages Improves Survival
Investigators report the discovery of a unique peptide sequence, M2pep, identified using a subtractive phage biopanning strategy against whole cells. The peptide preferentially binds to murine M2 cells, including tumor-associated macrophages, with low affinity for other leukocytes. [Proc Natl Acad Sci USA]
| Press Release

Interruption of Dendritic Cell-Mediated TIM-4 Signaling Induces Regulatory T Cells and Promotes Skin Allograft Survival
Scientists demonstrated that Ab blockade of dendritic cell-expressed TIM-4 leads to increased induction of induced regulatory T cells (iTregs) from naive CD4+ T cells, both in vitro and in vivo. iTreg induction occurs through suppression of IL-4/STAT6/Gata3-induced Th2 differentiation. [J Immunol] Abstract

EGFR Inhibitors Augment Antitumour Helper T-Cell Responses of HER Family-Specific Immunotherapy
Investigators report human epidermal receptor (HER) family epitopes that induced CD4 T-cell responses to head and neck squamous cell carcinoma (HNSCC). The results provide support for a novel strategy to treat HNSCC by combining epidermal growth factor receptor (EGFR)-targeted therapy with T-cell-based immunotherapy. [Brit J Cancer] Abstract

TLR7 Signaling Exacerbates CNS Autoimmunity through Downregulation of Foxp3+ Treg Cells
To define the contribution of Toll-like receptor 7 (TLR7) to the development of autoimmune encephalomyelitis, researchers evaluated the course of the disease in C57BL/6-Tlr7-deficient mice compared with that in wild type mice and found that TLR7-deficient mice had decreased disease severity. This protection was associated with decreased myelin oligodendrocyte glycoprotein-specific T-cell activation by primed dendritic cells, increased Foxp3+ regulatory T (Treg) cells in the periphery, decreased circulating autoantibodies, and attenuated inflammation within the central nervous system (CNS). [Eur J Immunol] Abstract

Mechanistic Model of Natural Killer Cell Proliferative Response to IL-15 Receptor Stimulation
Researchers developed a mathematical model to analyze the kinetic interactions that control the formation and localization of IL-15/IL-15R complexes. Their computational results demonstrated that IL-15/IL-15 receptor complexes on the cell surface were a key determinant of the magnitude of the IL-15 proliferative signal and that IL-15R occupancy functioned as an effective surrogate measure of receptor signaling. [PLoS Comput Biol] Full Article

IL-15 cis Presentation Is Required for Optimal NK Cell Activation in Lipopolysaccharide-Mediated Inflammatory Conditions
The authors showed that upon lipopolysaccharide or E. coli exposure, dendritic cells (DCs) produce three cytokines interleukin 2 (IL-2), IL-18, and interferon β (IFN-β) necessary and sufficient for natural killer (NK) cell activation. IFN-β enhances NK cell activation by inducing IL-15 and IL-15 receptor α not only in DCs but, surprisingly, also in NK cells. [Cell Rep] Abstract | Graphical Abstract | Full Article

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Antibody Therapeutics in Cancer
Monoclonal antibodies have entered the mainstream of cancer therapy. Their first use was as antagonists of oncogenic receptor tyrosine kinases, but today monoclonal antibodies have emerged as long-sought vehicles for the targeted delivery of potent chemotherapeutic agents and as powerful tools to manipulate anticancer immune responses. With ever more promising results from the clinic, the future will likely see continued growth in the discovery and development of therapeutic antibodies and their derivatives. [Science] Abstract

Regulatory T Cells in Nonlymphoid Tissues
The authors summarize recent findings in this new field, discussing knowns and unknowns about the origin, phenotype, function and memory of nonlymphoid tissue-resident Foxp3+CD4+ regulatory T cells.[Nat Immunol] Abstract

β-Arrestins 1 and 2 Are Critical Regulators of Inflammation
This review will focus on β-arrestins in immune cells and the impact of altered expression on the pathogenesis of specific inflammatory diseases. Understanding the role of β-arrestins in inflammation may lead to new strategies to treat inflammatory diseases, such as sepsis, rheumatoid arthritis, asthma, multiple sclerosis, inflammatory bowel disease and atherosclerosis. [Innate Immun] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation field.
Roche and Inovio Pharmaceuticals Partner on Inovio’s Prostate Cancer and Hepatitis B Immunotherapy Products
Roche and Inovio Pharmaceuticals, Inc. announced that they have entered into an exclusive worldwide license agreement to research, develop and commercialize Inovio’s highly-optimized, multi-antigen DNA immunotherapies targeting prostate cancer and hepatitis B. The licensed compounds are currently in preclinical development and have generated robust T-cell responses in animal models. [Inovio Pharmaceuticals, Inc.] Press Release

NIH Awards University of Chicago $1.5 Million to Study Novel Therapy for Multiple Sclerosis
Researchers from the University of Chicago have been awarded a five-year, $1.5 million grant from the National Institutes of Health (NIH) to develop stimulated dendritic cell-derived exosomes that show remarkable promise as a treatment for multiple sclerosis and other neurological diseases involving loss of myelin, the insulation around nerve fibers. [The University of Chicago] Press Release

NeoStem Announces Licensing of Treg Patents to Strengthen Autoimmune Platform
NeoStem, Inc. announced the licensing of three families of patents from the University of California, San Francisco (UCSF). NeoStem’s worldwide exclusive license to these patents provides incremental protection for the Company’s human Regulatory T cell (Treg) platform, and complements the recently announced collaboration with UCSF and the laboratories of Drs. Jeffrey Bluestone and Qizhi Tang, to develop Tregs for the treatment of type 1 diabetes, steroid resistant asthma, and organ transplant rejection. [NeoStem, Inc.] Press Release

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February 9-14, 2014
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Visit our events page to see a complete list of events in the immune regulation community.
Postdoctoral Fellowships – Immunology (Trinity College Dublin)

PhD/Postdoctoral Positions – Quantitative T-Cell Immunology (University of Leeds)

Postdoctoral Position – Identification of Novel Components of the Nlrp10 Pathway and their Effects on Dendritic Cell Mediated Immune Function (AstraZeneca)

Research Scientist – Immune System Signaling (University of Pennsylvania)

Postdoctoral Position – Innate Immune Signaling in the Developing Intestine (University of Connecticut Health Center)

Postdoctoral Fellowship – Immunology (Johns Hopkins University School of Medicine)

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

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Technologist – Mesenchymal Cell Research (STEMCELL Technologies Inc.)

Research Technologist – Cell Culture Media & Matrices (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

Quality Control Analyst – Media (STEMCELL Technologies Inc.)

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