Immune Regulation News Volume 5.01 | Jan 11 2013

Regulation of Dendritic Cell Activation by MicroRNA let-7c and BLIMP1
Mice with a dendritic cell (DC)-specific deletion of the transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp1) exhibit a lupus-like phenotype, secondary to enhanced DC production of IL-6. Here investigators explored further phenotypic changes in Blimp1-deficient DCs, the molecular mechanism underlying these changes, and their relevance to human disease. [J Clin Invest] Full Article

Specialized Role of Migratory Dendritic Cells in Peripheral Tolerance Induction
To examine the differential capacity of migratory dendritic cells (DCs) versus blood-derived lymphoid-resident DCs for Treg generation in vivo, scientists targeted a self antigen, myelin oligodendrocyte glycoprotein, using antibodies against cell surface receptors differentially expressed in these DC populations. [J Clin Invest] Full Article

Sortase-Mediated Modification of αDEC205 Affords Optimization of Antigen Presentation and Immunization against a Set of Viral Epitopes
A monoclonal antibody against the C-type lectin DEC205 (αDEC205) is an effective vehicle for delivery of antigens to dendritic cells through creation of covalent αDEC205-antigen adducts. These adducts can induce antigen-specific T-cell immune responses or tolerance. Researchers exploited the transpeptidase activity of sortase to install modified peptides and protein-sized antigens onto the heavy chain of αDEC205, including linkers that contain non-natural amino acids. [Proc Natl Acad Sci USA] Abstract | Press Release

HDAC Inhibition Suppresses Primary Immune Responses, Enhances Secondary Immune Responses, and Abrogates Autoimmunity during Tumor Immunotherapy
Investigators revealed an unexpected property of the histone deacetylase inhibitor (HDACi) MS-275 that enhances viral vector-induced lymphopenia leading to selective depletion of bystander lymphocytes and regulatory T cells while allowing expansion of antigen-specific secondary responses. [Mol Ther] Abstract

Role of TLR2-Dependent IL-10 Production in the Inhibition of the Initial IFN-γ T Cell Response to Porphyromonas gingivalis
As IL-10 and TLR2 are pivotal molecules in the immune response that P. gingivalis elicits, the authors hypothesized that TLR2-mediated IL-10 production, following the initial systemic exposure to P. gingivalis, inhibits the IFN-γ T cell response. [J Leukoc Biol] Abstract | Press Release

MicroRNA-126 Regulates the Induction and Function of CD4⁺ Foxp3⁺ Regulatory T Cells through PI3K/AKT Pathway
The authors showed that microRNA (miR)-126 could act as fine-tuner in regulation of PI3K-Akt pathway transduction in the induction and sustained suppressive function of regulatory T cells (Tregs) and provided a novel insight into the development of therapeutic strategies for promoting T-cell immunity by regulating Tregs through targeting specific miRNAs. [J Cell Mol Med] Abstract

miR-31 Regulates Interleukin 2 and Kinase Suppressor of Ras 2 during T Cell Activation
The contribution of microRNA (miR)-31 in T cell activation was investigated. miR-31 was upregulated during the activation of primary T lymphocytes upon T-cell receptor stimulation. Ectopic expression of miR-31 increased the expression of interleukin (IL)-2, while knockdown of endogenous miR-31 decreased the IL-2 expression. [Genes Immun] Abstract

CD134/CD137 Dual Costimulation-Elicited IFN-γ Maximizes Effector T-Cell Function but Limits Treg Expansion
To understand how immune stimulatory versus inhibitory components are regulated during CD134 plus CD137 dual costimulation (DCo), researchers utilized a model where DCo programs T-cells encountering a highly tolerogenic self-antigen to undergo effector differentiation. [Immunol Cell Biol] Abstract

Metabolic Regulation of T Lymphocytes
Investigators discuss the role of cellular metabolism in T cell development, activation, differentiation, and function to highlight the clinical relevance and opportunities for therapeutic interventions that may be used to disrupt immune pathogenesis. [Annu Rev Immunol] Abstract

IL-27 in Tumor Immunity and Immunotherapy
Interleukin (IL)-27 boosts antitumor immunity by contributing to the development of natural killer cells and cytotoxic T cells a central immunomodulatory effect and by exerting potent antiangiogenic and antimetastatic activities, a local antitumor effect. In this review, the authors argue that by virtue of its rate-limiting functions in innate and adaptive immune responses, modulating IL-27 holds considerable promise for future cancer immunotherapy. [Trends Mol Med] Abstract

Intestinal Dendritic Cells in Migrational Imprinting of Immune Cells
The authors provide an historic overview on the identification of the mechanisms controlling lymphocyte migration into the largest immune organ of the body, the gut, and they will describe how in recent years an unexpected role for dendritic cells has emerged as the architects in programming gut-homing immune cells. [Immunol Cell Biol] Abstract

Inovio Pharmaceuticals to Initiate Clinical Trial for Its Hepatitis C Therapeutic Vaccine (INO-8000) Later this Year
Inovio Pharmaceuticals, Inc. and its development partner VGX International, Inc. will move Inovio’s hepatitis C (HCV) DNA vaccine into a phase I/IIa clinical trial by the end of 2013. This advancement is based on outstanding results of a preclinical study which demonstrated for the first time that a multi-antigen SynCon® HCV vaccine can generate robust T-cell responses not only in the blood but, more importantly, in the liver, an organ known to suppress T-cell activity. [Inovio Pharmaceuticals, Inc.] Press Release

Daiichi Sankyo and Amplimmune Announce Strategic Alliance to Develop AMP-110 Therapy for Autoimmune Disease
Daiichi Sankyo, Co., Ltd. and Amplimmune, Inc. announced that they have entered into a broad strategic collaboration to develop a new therapeutic protein, AMP-110 (B7-H4 fusion protein).  The collaboration will focus on development of AMP-110, a potential immune modulation therapy for autoimmune diseases. [Daiichi Sankyo, Co., Ltd.] Press Release

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 Keystone Symposia on Molecular and Cellular Biology: Immune Activation in HIV Infection- Basic Mechanisms and Clinical Implications
April 3-8, 2013
Breckenridge, United States

Visit our events page to see a complete list of events in the immune regulation community.

Scientist or Engineer – hPSC Bioengineer (STEMCELL Technologies, Inc.)

Postdoctoral Fellowship – HIV Research  (Sandra Rotman Centre for Global Health)

Postdoctoral Position – Lupus and Immunology Research (University of Chicago)

Postdoctoral Position – Immune Regulation (Trinity College Dublin)

Postdoctoral Position – Immunobiology Using Advanced Fluorescence-Based Techniques (Karolinska Institute)

Associate Scientist – Clinical Immunology (Crucell Holland B.V.)

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

PhD Research Position – Regulation of Dendritic Cells and Their Progenitors in Infectious Diseases (University of Tübingen)

Postdoctoral Fellow – Transcriptional Regulation in CD8 T Lymphocytes (Université Libre de Bruxelles – Institute for Medical Immunology)

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