Immune Regulation News Volume 5.38 | Oct 4 2013

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]
Abstract | Full Article

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

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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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

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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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