Immune Regulation News Volume 5.07 | Feb 22 2013

Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA
Researchers found that mammalian cytosolic extracts synthesized cyclic guanosine monophosphate-adenosine monophosphate (cyclic GMP-AMP, or cGAMP) in vitro from adenosine triphosphate and guanosine triphosphate in the presence of DNA but not RNA. DNA transfection or DNA virus infection of mammalian cells also triggered cGAMP production. cGAMP bound to STING, leading to the activation of IRF3 and induction of interferon-β. [Science] Abstract | Press Release

Depletion of FOXP3+ Regulatory T Cells Promotes Hypercholesterolemia and Atherosclerosis
To define the role of FOXP3-expressing regulatory T cells (Tregs) in atherosclerosis, the authors used the DEREG mouse, which expresses the diphtheria toxin receptor under control of the Treg-specific Foxp3 promoter, allowing for specific ablation of FOXP3+ Tregs. [J Clin Invest] Full Article

Essential Requirement for IRF8 and SLC15A4 Implicates Plasmacytoid Dendritic Cells in the Pathogenesis of Lupus
In vitro evidence suggests that plasmacytoid dendritic cells are intimately involved in the pathogenesis of lupus. However, it remains to be determined whether these cells are required in vivo for disease development, and whether their contribution is restricted to hyperproduction of type I IFNs. To address this, researchers created lupus-predisposed mice lacking the IFN regulatory factor 8 (IRF8) or carrying a mutation that impairs the peptide/histidine transporter solute carrier family 15, member 4 (SLC15A4). [Proc Natl Acad Sci USA] Abstract

Interleukin-7 Facilitates HIV-1 Transmission to Cervico-Vaginal Tissue Ex Vivo
Scientists found that interleukin (IL)-7 significantly enhanced virus replication in ex vivo infected cervico-vaginal tissue. Similarly, they observed an enhancement of HIV-1 replication in lymphoid tissue explants. Analysis of T cells isolated from infected tissues showed that IL-7 reduced CD4⁺ T cell depletion preventing apoptosis, as shown by the decrease in the number of cells expressing the apoptotic marker APO2.7 and the increase in the expression of the anti-apoptotic protein B-cell lymphoma-2. [PLoS Pathog]
Abstract | Press Release

Mucosal Imprinting of Vaccine-Induced CD8⁺ T Cells Is Crucial to Inhibit the Growth of Mucosal Tumors
The authors identified a link between the route of vaccination and the induction of a mucosal homing program on induced CD8⁺ T cells that controlled their trafficking. [Sci Transl Med] Abstract

IGF-1 Promotes the Development and Cytotoxic Activity of Human NK Cells
Researchers identified an essential role for insulin-like growth factor 1 (IGF-1) in the positive regulation of human natural killer (NK) cell development and cytotoxicity. Specifically, they showed that human NK cells have the ability to produce IGF-1 and that differential endogenous IGF-1 expression leads to disparate cytotoxicity in human primary NK cells. [Nat Commun] Full Article

The Level of p38α MAPK Activation in Airway Epithelial Cells Determines the Onset of Innate Immune Responses to Planktonic and Biofilm Pseudomonas aeruginosa
Scientists report that in airway epithelial cells a threshold of p38α MAPK activation is required to trigger neutrophil recruitment, which is influenced by extrinsic and intrinsic factors. [J Infect Dis] Abstract

Tumor-Specific T Cells in Human Merkel Cell Carcinomas: A Possible Role for Tregs and T Cell Exhaustion in Reducing T Cell Responses
Merkel cell carcinomas (MCC) tumors were infiltrated by T cells, including effector, central memory and regulatory T cells (Tregs). Infiltrating T cells showed markedly reduced activation as evidenced by reduced expression of CD69 and CD25. Treatment of MCC tumors in vitro with IL-2 and IL-15 led to T cell activation, proliferation, enhanced cytokine production and loss of viable tumor cells from cultures. [J Invest Dermatol] Abstract

Imatinib Ameliorates Neuroinflammation in a Rat Model of Multiple Sclerosis by Enhancing Blood-Brain Barrier Integrity and by Modulating the Peripheral Immune Response
Researchers demonstrated that the small tyrosine kinase inhibitor imatinib enhances blood-brain barrier integrity in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Treatment was accompanied by decreased central nervous system inflammation and demyelination and especially reduced T-cell recruitment. [PLoS One] Full Article | Press Release

Transcriptional Regulation of Follicular T-Helper (Tfh) Cells
This review summarizes the recent progress in molecular mechanisms underlying Tfh differentiation and discusses the future perspectives for this important area of research. [Immunol Rev] Abstract

The Life of Regulatory T Cells
Antigen exposure and the presence of IL-2 are key determinants in the generation of memory Foxp3⁺ regulatory T (T_reg) cells. These results provide a foundation for studying the role of memory T_reg cells in controlling and treating autoimmune disorders and for testing the hypothesis that defects in the generation and maintenance of these cells underlie chronic, relapsing inflammatory diseases. [Ann NY Acad Sci] Abstract

Negative Regulatory Approaches to the Attenuation of Toll-Like Receptor Signaling
This review covers the modulation of toll-like receptor signaling at multiple levels, including adaptor complex destabilization, phosphorylation and ubiquitin-mediated degradation of signal proteins, manipulation of other receptors, and transcriptional regulation. Synthetic inhibitors are also briefly discussed to highlight negative regulatory approaches in the treatment of inflammatory diseases. [Exp Mol Med] Abstract

Xencor Initiates Phase Ib/IIa Trial of XmAbR5871 for Autoimmune Disease
Xencor, Inc. announced that the first patient has been dosed in a Phase Ib/IIa clinical trial of XmAb^®5871 in patients with moderate to severe rheumatoid arthritis. XmAb5871 is the first in a new class of therapeutic antibodies targeting the CD32b pathway in B cells, which shows potential to suppress autoimmune disorders without the side effects caused by B cell depletion. [Xencor, Inc.] Press Release

Immune Initiates Bertilimumab Phase II Clinical Trial in Ulcerative Colitis
Immune Pharmaceuticals Ltd. (Immune) and EpiCept announced that Immune is initiating a Phase II double-blind placebo controlled study with its lead drug, bertilimumab, in patients with moderate-to-severe ulcerative colitis. Bertilimumab is a first-in-class fully human monoclonal antibody targeting eotaxin-1, a chemokine small protein regulating eosinophilic inflammation. [Immune Pharmaceuticals Ltd.] Press Release

Coronado Biosciences Signs Research Collaboration and License Agreement with Freie Universität Berlin for Secretory Products of Trichuris suis
Coronado Biosciences, Inc. announced the signing of a sponsored research agreement and a joint ownership and exclusive license agreement with Freie Universität Berlin for the identification and evaluation of secretory proteins from Trichuris suis. The evaluation will be done in various pre-clinical in vitro and animal models which will further describe the mechanism of action for Trichuris suis ova and potentially lead to newly identified immune regulatory pharmaceutical agents. [Coronado Biosciences, Inc.] Press Release

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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 2nd Inflammatory & Immunological Biomarkers
March 20-22, 2013
San Francisco, United States

NEW 41^st Scandinavian Society for Immunology Meeting
April 14-17, 2013
Copenhagen, Denmark

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

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

Faculty Positions – Cancer Inflammation and Tolerance (Georgia Health Sciences University Cancer Center)

Postdoctoral Position – IL-17 and Inflammation Research (Hospices Civils de Lyon)

PhD Position – Mast Cells in HPV-Induced Skin Cancer (TU Dresden – Institute of Immunology)

PhD candidate – Immunoregulatory Properties of Stromal and Immune Cells (University of Saarland, Internal Medicine II)

Postdoctoral Position – NK/T Cells (The Ohio State University – Comprehensive Cancer Center)

Postdoctoral Position – Microbiota and Pro-Inflammatory Lymphoid Cells (Laboratory of Lymphoid Tissue Development, Institut Pasteur)

Research Specialist – Tolerance and Antirejection Techniques in Transplantation (University of Chicago)

Postdoctoral Position – Allo-Specific T Cell Tolerance (St. Anna Kinderkrebsforschung e.V.)

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