Volume 5.38 | Oct 4

Immune Regulation News 5.38 October 4, 2013
Immune Regulation News
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Defective Sphingosine 1-Phosphate Receptor 1 (S1P1) Phosphorylation Exacerbates TH17-Mediated Autoimmune Neuroinflammation
Phosphoproteomic analysis of multiple sclerosis brain lesions revealed S1P1 phosphorylation on S351, a residue crucial for receptor internalization. Mutant mice harboring an S1pr1 gene encoding phosphorylation-deficient receptors developed severe experimental autoimmune encephalomyelitis due to autoimmunity mediated by interleukin 17-producing helper T cells (TH17 cells) in the peripheral immune and nervous system. [Nat Immunol] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
MEF2 Is an In Vivo Immune-Metabolic Switch
Researchers used paired genetic and computational screens in Drosophila to identify transcriptional regulators of immunity and pathology and their associated target genes and physiologies. They showed that Mef2 is required in the fat body for anabolic function and the immune response. [Cell]
Full Article
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Control of T Helper 2 Responses by Transcription Factor IRF4-Dependent Dendritic Cells
The authors defined a specific dendritic cell subset that is involved in T helper 2 (Th2) cell differentiation in vivo in response to a protease allergen, as well as infection with Nippostrongylus brasiliensis. They demonstrated that this subset is controlled by the transcription factor interferon regulatory factor 4 (IRF4), which is required for their differentiation and Th2 cell-inducing function. [Immunity] Abstract

Liver Type I Regulatory T Cells Suppress Germinal Center Formation in HBV-Tolerant Mice
Scientists investigated the unknown mechanisms of liver tolerance by using an established hepatitis B virus (HBV)-carrier mouse model, and found that these mice exhibited an antigen-specific tolerance toward peripheral HBsAg vaccination, showing unenlarged draining lymph node, lower number of germinal centers (GC), and inactivation of GC B cells and follicular T helper cells. [Proc Natl Acad Sci USA] Abstract

NF-κB Inhibitor Targeted to Activated Endothelium Demonstrates a Critical Role of Endothelial NF-κB in Immune-Mediated Diseases
Researchers demonstrated that cell type-specific nuclear transcription factor κB (NF-κB) inhibition can be achieved using multi-modular fusion proteins, which exclusively target activated endothelial cells. Inhibition of NF-κB within activated endothelium potently ameliorated peritonitis and arthritis in mice, indicating that endothelial NF-κB might be a valid target in inflammatory diseases. [Proc Natl Acad Sci USA]
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Enhancement of Antitumor Immunity in Lung Cancer by Targeting Myeloid-Derived Suppressor Cell Pathways
Using a murine model of lung cancer, the authors demonstrated that a combination treatment with gemcitabine and a superoxide dismutase mimetic targets immunosuppressive myeloid-derived suppressor cells in the tumor microenvironment and enhances the quantity and quality of both effector and memory CD8+ T cell responses. [Cancer Res] Abstract

Soluble Factors Secreted by T-Cells Promote β-Cell Proliferation
Investigators report that islets exhibiting insulitis also manifested proliferation of β-cells which positively correlated with the extent of lymphocyte infiltration. Adoptive transfer of diabetogenic CD4+ and CD8+ T-cells, but not B-cells, selectively promoted β-cell proliferation in vivo independent from the effects of blood glucose, circulating insulin or by modulating apoptosis. [Diabetes] Abstract | Press Release

Jak/STAT and PI3K Signaling Pathways Have Both Common and Distinct Roles in IL-7-Mediated Activities in Human CD8+ T Cells
It was hypothesized that IL-7-induced signaling molecules could be linked with distinct IL-7-associated activities. To address this, the activation and functional associations of IL-7-induced signaling pathways, specifically antigen-independent activities that are relevant to T cell homeostasis, were examined. [J Leukoc Biol] Abstract

RGS3 Controls T Lymphocyte Migration in a Model of Th2-Mediated Airway Inflammation
Regulators of G protein signaling (RGS) proteins modulate G protein signaling; however, their role in the regulation of adaptive immune responses has not been thoroughly explored. Investigators demonstrated abundant expression of the Gi/Gq-specific RGS3 in activated T cells, and that diminished RGS3 expression in a T cell thymoma increased cytokine-induced migration. [Am J Physiol Lung Cell Mol Physiol] Abstract

In Vivo Action of IL-27: Reciprocal Regulation of Th17 and Treg Cells in Collagen-Induced Arthritis
The authors investigated the in vivo effects of interleukin (IL)-27 on arthritis severity in a murine collagen-induced arthritis model and its mechanism of action regarding control of regulatory T (Tregs) and IL-17-producing T helper 17 (Th17) cells. [Exp Mol Med] Full Article

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Current Status of Interleukin-10 and Regulatory T-Cells in Cancer
Tumor growth elicits antigen-specific cytotoxic as well as immune suppressive responses. Interleukin-10 (IL-10) is a key immune-suppressive cytokine produced by regulatory T-cells and by helper T-cells. Here, the authors review pleiotropic functions of IL-10 that impact the immune pathology of cancer. [Curr Opin Oncol] Abstract

Immunotherapeutics for Breast Cancer
The authors review recent advances leading to a new understanding of immunology of breast cancer with its potential clinical applications. [Curr Opin Oncol] Abstract

Regulatory Mechanisms that Control T-Follicular Helper and T-Helper 1 Cell Flexibility
During the commitment process, helper T cells need to integrate both signals derived from the T-cell receptor and from the surrounding microenvironment. These external signals are then translated into internal changes in gene expression potential to ultimately define the functional characteristics of the cell. The authors discuss this topic from the perspective of T-follicular helper and T-helper type 1 cell differentiation. [Immunol Cell Biol] Abstract

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NewLink Genetics Presents Data Demonstrating Potential Chemo-Sensitization Activity of Its HyperAcute™ Cancer Immunotherapy Product Candidates
NewLink Genetics Corporation announced the presentation of data on its lead HyperAcute cancer immunotherapy product candidates. NewLink researchers presented data showing greater than expected responses to salvage chemotherapy following treatment with both algenpantucel-L in patients with pancreatic cancer and tergenpumatucel-L in patients with non-small cell lung cancer. [Press release from NewLink Genetics Corporation discussing research presented at the 2013 European Cancer Congress (ESMO), Amsterdam] Press Release

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NW Bio Activates Second Site in DCVax-Direct Phase I/II Trial
Northwest Biotherapeutics (NW Bio) announced that the MD Anderson Cancer Center Orlando has become the second site participating in the Phase I/II clinical trial of DCVax-Direct, the company’s next generation dendritic cell product for the potential treatment of all inoperable solid tumor cancers. [Northwest Biotherapeutics] Press Release

Researchers at University of Coimbra, Portugal, Win the Astellas European Foundation’s Inaugural Uro-Oncology Grant
The Astellas European Foundation announced that Dr. Celia Gomes from the University of Coimbra has been selected as the recipient of the inaugural Uro-Oncology Grant 2013. The $150,000 award will support the University of Coimbra’s team looking at natural killer cell-based adoptive therapy targeting human bladder cancer stem cells: impact on tumor progression using a humanized orthotopic animal model. [PR Newswire Association LLC] Press Release

Medistem Announces Preclinical Data on Type 1 Diabetes and Filing of Intellectual Property
Medistem, Inc. announced that it filed patent application #61/885909 covering immune modulatory aspects of ERC-124, the Company’s clinical-stage stem cell product. The patent application includes data that defines the mechanism by which ERC-124 therapy prevented Type 1 Diabetes and other autoimmune conditions in animal models. Specifically, the animal study demonstrated that ERC-124 activates T regulatory cells, a cell type known to block autoimmunity by controlling pathological autoreactive T cells. [GlobeNewswire, Inc.] Press Release
US Government Shuts Down
The US government entered a state of suspended animation on 1 October after Congress failed to agree on a budget for the next fiscal year, causing federal agencies – including those overseeing science policy and research – to shut down indefinitely. Most government scientists were ordered to stay at home, their offices and labs closed or run by a skeleton staff of ‘essential’ workers. The National Institutes of Health and the National Science Foundation stopped processing grants, some government websites were made inaccessible and many important research programmes were left hanging, potentially putting lives at risk in the case of some disease studies. [Nature News] Editorial

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW World Vaccine Congress 2013
March 24-26, 2014
Washington, United States

NEW Immunochemistry & Immunobiology: Re-Evaluating the Fundamentals of Immunology, Their Clinical Potentials, Their Meaningful Measures, and the Unmet Needs
June 1-6, 2014
Newry, United States

Visit our events page to see a complete list of events in the immune regulation community.
NEW Senior Principal Scientist – Immunology (Johnson & Johnson)

NEW Postdoctoral Fellow – Ripk1 in Innate Immune Responses and Necroptosis (University of Massachusetts Medical School)

PhD Position – T-Lymphocyte Antigen Recognition (Medical University of Vienna)

Research Fellow – Immunology (Queen’s University Belfast)

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

Research Scientist – Immune System Signaling (University of Pennsylvania)

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.)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

Quality Control Analyst – Media (STEMCELL Technologies Inc.)

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