Immune Regulation News Volume 4.49 | Dec 21 2012

Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA
Cytosolic DNA induces type I interferons and other cytokines that are important for antimicrobial defense but can also result in autoimmunity. This DNA signaling pathway requires the adaptor protein STING and the transcription factor IRF3, but the mechanism of DNA sensing is unclear. Here, researchers showed that mammalian cytosolic extracts synthesized cyclic GMP-AMP in vitro from ATP and GTP in the presence of DNA but not RNA. [Science] Abstract | Press Release

Combinatorial Antigen Recognition with Balanced Signaling Promotes Selective Tumor Eradication by Engineered T Cells
Investigators present a strategy to render T cells specific for a tumor in the absence of a truly tumor-restricted antigen. T cells are transduced with both a chimeric antigen receptor that provides suboptimal activation upon binding of one antigen and a chimeric costimulatory receptor that recognizes a second antigen. [Nat Biotechnol] Abstract | Press Release

Crosstalk between Neutrophils, B-1a Cells and Plasmacytoid Dendritic Cells Initiates Autoimmune Diabetes
Scientists showed that in young female nonobese diabetic mice, physiological beta cell death induces the recruitment and activation of B-1a cells, neutrophils and plasmacytoid dendritic cells to the pancreas. [Nat Med] Abstract | Press Release

Up-Regulation of a Death Receptor Renders Antiviral T Cells Susceptible to NK Cell-Mediated Deletion
Antiviral T cell responses in hepatotropic viral infections such as hepatitis B virus are profoundly diminished and prone to apoptotic deletion. Here, researchers investigated whether the large population of activated NK cells in the human liver contributes to this process. [J Exp Med] Abstract

Treg-Mediated Suppression of Atherosclerosis Requires MYD88 Signaling in DCs
Given the expansion of CD11c⁺ DCs during the progression of atherosclerosis and the key role of T cell activation in atherogenesis, scientists sought to understand the role of TLR signaling in CD11c⁺ DCs in atherosclerosis. [J Clin Invest] Full Article | Press Release

Siglec-1 Is a Novel Dendritic Cell Receptor that Mediates HIV-1 Trans-Infection through Recognition of Viral Membrane Gangliosides
The authors showed that the sialic acid-binding Ig-like lectin 1 (Siglec-1), which is highly expressed on mature dendritic cells, specifically binds HIV-1 and vesicles carrying sialyllactose. [PLoS Biol]
Full Article | Press Release

Interferon-γ Mediates Chemokine-Dependent Recruitment of Natural Killer Cells during Viral Infection
Natural killer (NK) cells provide in vivo control of orthopoxvirus infections in association with their expansion in the draining lymph node, where they are normally very rare. Herein, investigators determined that NK-cell depletion results in enhanced infection following footpad inoculation of cowpox virus, a natural pathogen of rodents. [Proc Natl Acad Sci USA] Abstract

The Depletion of NK Cells Prevents T Cell Exhaustion to Efficiently Control Disseminating Virus Infection
The authors examined the frequency of NK cells and their influence on T cell responses in mice given variants of lymphocytic choriomeningitis virus that cause acute or persisting infection. [J Immunol] Abstract

Role of the NK Cell-Activating Receptor CRACC in Periodontitis
Investigators showed that the predominant NK cell-activating molecule in periodontitis is CD2-like receptor activating cytotoxic cells (CRACC). They demonstrated that CRACC induction was significantly more pronounced in aggressive than chronic periodontitis and correlated positively with periodontal disease severity, subgingival levels of specific periodontal pathogens, and NK cell activation in vivo. [Infect Immun] Abstract

Activation of Invariant NKT Cells with Glycolipid Ligand α-Galactosylceramide Ameliorates Glucose-6-Phosphate Isomerase Peptide-Induced Arthritis
Researchers investigated the roles of activation of invariant natural killer T cells by alpha-galactosylceramide in glucose-6-phosphate isomerase peptide-induced arthritis. [PLoS One] Full Article

Cell-Extrinsic Effects of Tumor ER Stress Imprint Myeloid Dendritic Cells and Impair CD8⁺ T Cell Priming
Tumor-infiltrating myeloid cells, such as dendritic cells (BMDC), are key regulators of tumor growth. However, the tumor-derived signals polarizing BMDC to a phenotype that subverts cell-mediated anti-tumor immunity have yet to be fully elucidated. Addressing this problem, the authors showed that the tumor unfolded protein response can function in a cell-extrinsic manner via the transmission of ER stress to BMDC. [PLoS One]
Full Article | Press Release

Oncomatrix Signs an Agreement with the University of Stuttgart to Develop New Drugs for Treating Tumor Metastases
Oncomatrix has signed an agreement with the University of Stuttgart to develop new drugs with tumor targeted activity. This partnership will allow the development of immunoconjugates able to attack the cells involved in metastasis in invasive breast and pancreas cancers. [Business Wire Newsroom] Press Release

Soligenix Expands Pipeline with Acquisition of Novel Innate Defense Regulator Clinical Program
Soligenix, Inc. announced the acquisition of a novel drug technology, known as SGX94, representing a unique approach to modulation of the innate immune system. SGX94 is an innate defense regulator that regulates the innate immune system to reduce inflammation, eliminate infection and enhance tissue healing by binding to the pivotal regulatory protein p62, also known as sequestosome-1. [Soligenix, Inc.]
Press Release

FDA Approves Biotest’s BIVIGAM™, an Intravenous Immune Globulin (Human), 10% Liquid
Biotest AG announced that Biotest Pharmaceuticals Corporation received approval for BIVIGAM™ for the treatment of patients with primary humoral immunodeficiency from the U.S. Food and Drug Administration (FDA). [Biotest AG] 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)

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Therapeutic Goods Administration (Australia)

NEW Keystone Symposia: Myeloid Cells: Regulation and Inflammation
February 19-24, 2013
Keystone, United States

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