Volume 5.35 | Sep 13

Immune Regulation News 5.35 September 13, 2013
Pulmonary Cell News
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Cytoplasmic LPS Activates Caspase-11: Implications in TLR4-Independent Endotoxic Shock
Researchers report that contamination of the cytoplasm by lipopolysaccharide (LPS) is the signal that triggers caspase-11 activation in mice. Specifically, caspase-11 responds to penta- and hexa-acylated lipid A, whereas tetra-acylated lipid A is not detected, providing a mechanism of evasion for cytosol-invasive Francisella. [Science] Abstract | Press Release
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PUBLICATIONS (Ranked by impact factor of the journal)
Fatty Acid-Induced Mitochondrial Uncoupling Elicits Inflammasome-Independent IL-1α and Sterile Vascular Inflammation in Atherosclerosis
The authors found that atherogenesis was mediated by IL-1α and they identified fatty acids as potent inducers of IL-1α-driven vascular inflammation. Fatty acids selectively stimulated the release of IL-1α but not of IL-1β by uncoupling mitochondrial respiration. [Nat Immunol] Abstract

Minimal Differentiation of Classical Monocytes as They Survey Steady-State Tissues and Transport Antigen to Lymph Nodes
Researchers showed that Ly-6C+ monocytes constitutively trafficked into skin, lung, and lymph nodes (LNs). Entry was unaffected in gnotobiotic mice. Monocytes in resting lung and LN had similar gene expression profiles to blood monocytes but elevated transcripts of a limited number of genes including cyclo-oxygenase-2 and major histocompatibility complex class II, induced by monocyte interaction with endothelium. [Immunity] Abstract

Histone Methyltransferase Ash1l Suppresses Interleukin-6 Production and Inflammatory Autoimmune Diseases by Inducing the Ubiquitin-Editing Enzyme A20
Investigators report that Ash1l, a H3K4 methyltransferase, suppressed interleukin-6, and tumor necrosis factor production in Toll-like receptor-triggered macrophages, protecting mice from sepsis. [Immunity] Abstract

MicroRNA-146a Regulates Survival and Maturation of Human Plasmacytoid Dendritic Cells
The authors investigated the role of microRNA-146a (miR-146a) in Toll-like-receptor (TLR) pathway regulation in human plasmacytoid dendritic cells (pDCs). They showed that miR-146a expression was induced upon TLR7/9 signaling. Furthermore, ectopic miR-146a expression effectively impaired TLR-mediated signaling in pDCs as TLR-induced NF-κB activation was reduced. [Blood] Abstract

PDCD5 Negatively Regulates Autoimmunity by Upregulating FOXP3+ Regulatory T Cells and Suppressing Th17 and Th1 Responses
Researchers demonstrated that PDCD5 interacts with FOXP3, increases acetylation of FOXP3 in synergy with Tip60 and enhances the repressive function of FOXP3. In PDCD5 transgenic mice, overexpression of PDCD5 enhanced the level of FOXP3 protein and percentage of CD4+CD25+FOXP3+ cells. [J Autoimmune] Abstract

The Scaffold Protein Prohibitin Is Required for Antigen-Stimulated Signaling in Mast Cells
The authors found that prohibitin (PHB) was abundant in the intracellular granules of mast cells, which are critical for allergic responses to antigens. Thus, they investigated whether PHB played a role in signaling mediated by the high-affinity receptor for antigen-bound immunoglobulin E, FcεRI. [Sci Signal] Abstract

A Transient Reversal of miRNA-Mediated Repression Controls Macrophage Activation
Investigators showed that there is a transient reversal of miRNA-mediated repression during the early phase of the inflammatory response in macrophages, which leads to the protection of cytokine mRNAs from miRNA-mediated repression. [EMBO Rep] Abstract

CD8+ Cells Regulate the T Helper-17 Response in an Experimental Murine Model of Sjögren Syndrome
This study investigated the regulatory function of CD8+ cells in T helper-17 cell-mediated corneal epithelial barrier disruption that develops in a murine desiccating stress model that resembles Sjögren syndrome. [Mucosal Immunol] Abstract

Inactivation of Tumor-Specific CD8+ CTLs by Tumor-Infiltrating Tolerogenic Dendritic Cells
Scientists found that Hepa1-6-1 had the ability to grow continuously after subcutaneous implantation into syngeneic C57BL/6 mice and did not prime CD8+ cytotoxic T lymphocytes (CTLs). In contrast, Hepa1-6-2 cells, which display reduced levels of adhesion molecules, such as Intercellular Adhesion Molecule 1, failed to grow in vivo and efficiently primed CTLs. [Immunol Cell Bio] Full Article
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Transcriptional Control of Regulatory T Cell Development and Function
Findings reveal that regulatory T cell lineage commitment is not only controlled by genetic and epigenetic imprinting, but also modulated by transcriptional programs responding to extracellular signals. [Trends Immunol] Abstract

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First Study to Investigate the Human Genome in Multiple Sclerosis
The National Institutes of Health awarded Benaroya Research Institute at Virginia Mason a $1.9 million grant to find marks in the human genome which can explain why some white blood cells cause damage to the spinal cord and brain in multiple sclerosis (MS). This is the first study to look for molecular changes in the genome of specific immune cells responsible for the devastation caused by MS. [Benaroya Research Institute at Virginia Mason] Press Release

VolitionRx-Led Consortium Awarded €780 000 Eurostars Grant
VolitionRx Limited is lead partner of a consortium in a project valued at €779,493 under the EUREKA Eurostars scheme. The project aims to develop new applications of the Nucleosomics biomarker technology in inflammatory disease. VolitionRx’s contribution to the project is to develop novel NuQ® biomarkers for immune response. [VolitionRx Limited] Press Release

Adaptive Biotechnologies Receives $2.53 Million Phase II SBIR to Develop Test to Identify Cancer Patients at Risk of Death by Infection after Cord Blood Transplants
Adaptive Biotechnologies announced that it received a $2.53 million Phase II Small Business Innovation Research (SBIR) award from the National Heart, Lung, and Blood Institute, a division of the NIH, to commercialize a test to measure the ability of a cancer patient’s adaptive immune system to fight infection after a cord blood transplant. [PR Newswire Association LLC] Press Release

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NEW Interleukin 6: Biology-Pathophysiology-Therapy
May 14-17, 2014
Kiel, Germany

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NEW Research Technician – Cancer Immunotherapy (The Netherlands Cancer Institute [NKI-AvL])

Postdoctoral Fellowships – Immunology (Trinity College Dublin)

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

Postdoctoral Position – Identification of Novel Components of the Nlrp10 Pathway and their Effects on Dendritic Cell Mediated Immune Function (AstraZeneca)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Scientist – Immune System Signaling (University of Pennsylvania)

Postdoctoral Position – Innate Immune Signaling in the Developing Intestine (University of Connecticut Health Center)

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)

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