Human Immunology News Volume 1.07 | Apr 30 2013

Coexpression of CD49b and LAG-3 Identifies Human and Mouse T Regulatory Type 1 Cells
By gene expression profiling of human CD4⁺ type 1 T regulatory (Tr1) cell clones, the authors identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells. They showed the specificity of these markers in mouse models of intestinal inflammation and helminth infection and in the peripheral blood of healthy volunteers. [Nat Med] Abstract

PUBLICATIONS (Ranked by impact factor of the journal)

Characterization of Pathogenic Human Monoclonal Autoantibodies against GM-CSF
The authors generated 19 monoclonal autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) from six patients with idiopathic pulmonary alveolar proteinosis. The autoantibodies used multiple V genes, excluding preferred V-gene use as an etiology, and targeted at least four nonoverlapping epitopes on GM-CSF, suggesting that GM-CSF is driving the autoantibodies and not a B-cell epitope on a pathogen cross-reacting with GM-CSF. [Proc Natl Acad Sci USA] Abstract

Genome-Wide DNA Methylation Study Suggests Epigenetic Accessibility and Transcriptional Poising of Interferon-Regulated Genes in Naïve CD4+ T Cells from Lupus Patients
Scientists performed a genome-wide DNA methylation study in two independent sets of lupus patients and matched healthy controls to characterize the DNA methylome in naïve CD4+ T cells in lupus. [J Autoimmun] Abstract

Therapeutic Regulation of Myeloid-Derived Suppressor Cells and Immune Response to Cancer Vaccine in Patients with Extensive Stage Small Cell Lung Cancer
In a clinical trial of patients with extensive stage small cell lung cancer (SCLC), scientists tested the possibility that targeting myeloid-derived suppressor cells can improve the induction of immune responses by a cancer vaccine. [Cancer Immunol Immunother] Abstract

Immune Complexes Activate Human Endothelium Involving the Cell-Signaling High-Mobility Group Box 1 Protein-RAGE Axis in the Pathogenesis of Lupus Vasculitis
Researchers demonstrated for the first time that immune complexes upregulated cell surface expression of the receptor for advanced glycation end products (RAGE), the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, increased the secretion of the chemokines interleukin 8, monocyte chemoattractant protein-1, the proinflammatory cytokines interleukin 6, tumor necrosis factor-α and promoted the activation of the transcription factor NF-κB p65 in human endothelial cells. [Lab Invest] Abstract

Circulating CD4+ and CD8+ T Cells Are Activated in Inflammatory Bowel Disease and Are Associated with Plasma Markers of Inflammation
The authors evaluated the role of chronic inflammation on circulating T cell activation in human subjects with Crohn’s Disease and ulcerative colitis. [Immunology] Abstract

Derailed B Cell Homeostasis in Patients with Mixed Connective Tissue Disease
Investigators aimed to determine phenotypic abnormalities of peripheral B cell subsets in mixed connective tissue disease (MCTD). Blood samples were obtained from 46 MCTD patients, and 20 controls. [Hum Immunol] Abstract

MRP8 Promotes Th17 Differentiation via Upregulation of IL-6 Production by Fibroblast-Like Synoviocytes in Rheumatoid Arthritis
Researchers investigated whether the level of myeloid-related protein (MRP)8/MRP14 is positively associated with interleukin (IL)-6 and IL-17 levels in rheumatoid arthritis (RA) synovial fluid (SF) and found that MRP8/MRP14 level had a significant correlation with IL-6 and IL-17 levels in RA SF. They also observed that MRP8-induced IL-17 production by peripheral blood mononuclear cells but MRP14 did not. [Exp Mol Med] Full Article

Silencing of Indoleamine 2,3-Dioxygenase Enhances Dendritic Cell Immunogenicity and Antitumor Immunity in Cancer Patients
Scientists investigated the safety, immunogenicity and clinical response of indoleamine 2,3-dioxygenase-silenced dendritic cell vaccine in four patients with gynecological cancers. [Int J Oncol] Abstract

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CD40 Immunotherapy for Pancreatic Cancer
The authors describe both laboratory and clinical efforts to target the CD40 pathway for immunotherapy in pancreatic ductal adenocarcinoma. Findings suggest that CD40 agonists can mediate both T-cell-dependent and T-cell-independent immune mechanisms of tumor regression in mice and patients. [Cancer Immunol Immunother] Abstract

Detecting Multiple Autoantibodies to Diagnose Autoimmune Co-Morbidity (Multiple Autoimmune Syndromes and Overlap Syndromes): A Challenge for the Autoimmunologist
This review highlights the importance of multiple antibody assays in the diagnosis of multiple autoimmune and overlap syndromes and summarizes the general conditions of autoantibody detection using the model of the five W’s: why, who, what, when and where. [Immunol Res] Abstract

Autoimmunity in Immunodeficiency
Although much of our understanding comes from data gathered through experimental models, there are several well-characterized primary immunodeficiencies that have improved our knowledge of the pathways that drive autoimmunity. This review discusses these immunodeficiencies and reviews the literature with respect to the proposed mechanisms for autoimmunity within each put forth to date. [Curr Allergy Asthma Rep] Abstract

Visit our reviews page to see a complete list of reviews in the human immunology research field.

Merck Invests in Pan-Canadian Life Sciences Research Innovation Sector
Merck Canada announced at the BIO International Convention that it is reinforcing its commitment to the Canadian life sciences research innovation sector. Merck will provide $4 million in funding to the Institute for Research in Immunology and Cancer – Commercialization of Research for future corridor projects developed in collaboration with two other Canadian Centres of Excellence for Commercialization and Research based in Ontario and in British Columbia. [Merck Canada Inc.] Press Release

Opsona Therapeutics Limited Raises €33 Million (USD 43 Million) Oversubscribed Series C Equity Financing to Advance Clinical Development of Its Lead Product OPN- 305
Opsona Therapeutics Limited (Opsona) announced that it has raised €33 million in an oversubscribed Series C financing. Opsona is developing new treatments for inflammatory diseases and will use the proceeds to conduct a two-part multi-centered, double blinded and placebo controlled clinical study to evaluate the safety, tolerability and efficacy of its lead product OPN-305 in renal transplant patients at high risk of Delayed Graft Function. [Opsona Therapeutics Limited] Press Release

Sareum and SRI International Announce Agreement to Advance Development of Tyrosine Kinase 2 Inhibitors for Treatment of Autoimmune and Inflammatory Diseases
Sareum has entered a co-development agreement with independent nonprofit research and development institute SRI International to advance Sareum’s Tyrosine Kinase 2 small molecule drug discovery program for readiness in human clinical trials. [Sareum Holdings plc] Press Release

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NEW IMMUNOLOGY2013™, The AAI (American Association of Immunologists) Annual Meeting
May 3-7, 2013
Honolulu, United States

NEW 27^th European Immunogenetics and Histocompatibility Conference
May 11-14, 2013
Maastricht, Netherlands

Visit our events page to see a complete list of events in the human immunology community.

NEW Faculty Position – Cancer Immunology (Mayo Clinic)

NEW Research Fellow (King’s College London)

Scientist – Immunology (Crucell Holland B.V.)

Physician/Scientist – Tumor Immunotherapy (Stanford University School of Medicine)

Postdoctoral Fellow – Cancer Immunology (Dana-Farber Cancer Institute / Harvard Medical School)

PhD Studentship (University of Lübeck, ISEF)

Postdoctoral Position – Basic Diabetes Research (Université Libre de Bruxelles)

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