Volume 5.05 | Feb 8

Immune Regulation News 5.05 February 8, 2013
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
Mcl-1 Is Essential for the Survival of Plasma Cells
Scientists found that deletion of the gene encoding the antiapoptotic protein Mcl-1 in plasma cells resulted in rapid depletion of this population in vivo. [Nat Immunol] Abstract | Press Release

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PUBLICATIONS (Ranked by impact factor of the journal)

Two-Photon Imaging of Phagocyte-Mediated T Cell Activation in the CNS
To visualize T cell activation in the CNS, investigators introduced a truncated fluorescent derivative of nuclear factor of activated T cells as a real-time T cell activation indicator. In experimental autoimmune encephalomyelitis, a rat model of multiple sclerosis, they tracked T cells interacting with structures of the vascular blood-brain barrier. [J Clin Invest] Full Article

Amelioration of Arthritis through Mobilization of Peptide-Specific CD8+ Regulatory T Cells
The murine MHC class Ib molecule Qa-1b (HLA-E in humans) exhibits limited polymorphisms and binds to two dominant self peptides: Hsp60p216 and Qdm. Investigators found that peptide-induced expansion of tetramer-binding CD8+ regulatory T cells that recognize Qa-1-Hsp60p216 but not Qa-1-Qdm strongly inhibited collagen-induced arthritis, an animal model of human rheumatoid arthritis. [J Clin Invest]
Abstract | Press Release

Essential Requirement for IRF8 and SLC15A4 Implicates Plasmacytoid Dendritic Cells in the Pathogenesis of Lupus
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). IRF8-deficient NZB mice, lacking plasmacytoid dendritic cells, showed almost complete absence of anti-nuclear, anti-chromatin, and anti-erythrocyte autoantibodies, along with reduced kidney disease. [Proc Natl Acad Sci USA] Abstract | Press Release

H-Y Antigen-Binding B Cells Develop in Male Recipients of Female Hematopoietic Cells and Associate with Chronic Graft vs. Host Disease
The authors previously showed that IgG allo-antibodies recognize Y chromosome-encoded proteins (H-Y) and a dominant H-Y epitope, DEAD box protein (DBY-2) detectable 6-12 months after transplant in male patients who receive grafts from female donors (F→M) in hematopoietic cell transplantation (HCT). Here they present FACS studies of peripheral blood mononuclear cells collected 6 months after transplant showing that 16 of 28 F→M HCT patients have circulating donor B cells that express B-cell receptor specific for DBY-2. The detection of these DBY-2 B cells 6 months after HCT are associated with chronic graft vs. host disease development. [Proc Natl Acad Sci USA] Abstract | Press Release

Functional Characterization of HLA-G+ Regulatory T Cells in HIV-1 Infection
Researchers showed that non-classical HLA-G-expressing CD4 regulatory T cells are highly susceptible to HIV-1 infection and significantly reduced in persons with progressive HIV-1 disease courses. Moreover, the proportion of HLA-G+ CD4 and CD8 T cells was inversely correlated to markers of HIV-1 associated immune activation. [PLoS Pathog] Full Article

Langerhans Cells Favor Skin Flora Tolerance through Limited Presentation of Bacterial Antigens and Induction of Regulatory T Cells
Using monocyte-derived and skin-derived dendritic cells (DCs), scientists demonstrated that epidermal langerhans cells, the DCs in the most superficial layer of the skin, have a poor capacity to internalize bacteria because of low expression of FcγRIIa. [J Invest Dermatol] Abstract

TLR-2 Activation Induces Regulatory T Cells and Long-Term Suppression of Asthma Manifestations in Mice
Researchers aimed to test whether long-term suppression of asthma manifestations can be achieved by locally expanding the T regulatory cell subset via intranasal administration of a TLR-2 agonist. [PLoS One] Full Article

Rhamnogalacturonan II Is a Toll-Like Receptor 4 Agonist that Inhibits Tumor Growth by Activating Dendritic Cell-Mediated CD8+ T Cells
The authors evaluated the effectiveness of rhamnogalacturonan II-stimulated bone marrow-derived dendritic cells vaccination on the induction of antitumor immunity in a mouse lymphoma model using EG7-lymphoma cells expressing ovalbumin. [Exp Mol Med] Full Article

ZIP8 Regulates Host Defense through Zinc-Mediated Inhibition of NF-κB
Previous studies suggest that zinc may regulate NF-κB activity during innate immune activation, but a mechanistic basis to support this has been lacking. Here scientists report that the zinc transporter SLC39A8 (ZIP8) is a transcriptional target of NF-κB and functions to negatively regulate proinflammatory responses through zinc-mediated down-modulation of IκB kinase activity in vitro. [Cell Rep]
Full Article | Graphical Abstract | Press Release

Autologous Lysate-Pulsed Dendritic Cell Vaccination followed by Adoptive Transfer of Vaccine-Primed Ex Vivo Co-Stimulated T Cells in Recurrent Ovarian Cancer
The authors report a combinatorial approach encompassing dendritic cell-based autologous whole tumor vaccination and anti-angiogenesis therapy, followed by the adoptive transfer of autologous vaccine-primed CD3/CD28-co-stimulated lymphocytes. [OncoImmunology] Abstract | Press Release

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REVIEWS

Circadian Control of the Immune System
Circadian rhythms, which have long been known to play crucial roles in physiology, are emerging as important regulators of specific immune functions. This review summarizes the current knowledge of circadian rhythms in the immune system and provides an outlook on potential future implications. [Nat Rev Immunol] Abstract

Dendritic Cells and the Promise of Antigen-Specific Therapy in Rheumatoid Arthritis
The authors discuss the current understanding of autoantigens and their relationship to immunopathogenesis of rheumatoid arthritis (RA), and emerging therapeutics that aim to leverage normal tolerance mechanisms for implementation of antigen-specific therapy in RA. [Arthritis Res Ther] Abstract

Imaging Natural Killer T Cells in Action

This review attempts to highlight some of the recent studies that use in vivo imaging technologies to address natural killer T cell responses in a variety of animal models. [Immunol Cell Biol] Abstract

INDUSTRY NEWS

Aduro Announces Acquisition of GVAX Assets from BioSante
Aduro BioTech, Inc. announced the acquisition of all GVAX assets from BioSante Pharmaceuticals, Inc., including intellectual property and cell lines. This acquisition substantially expands Aduro’s immunotherapy portfolio and strengthens its competitive position in the field. [Business Wire] Press Release

Merck Serono and Opexa Therapeutics Enter into Option and License Agreement for Development of Tcelna™ (imilecleucel-T) for Treatment of Multiple Sclerosis

Opexa Therapeutics, Inc. announced the execution of an agreement with Merck Serono for the development and commercialization of Tcelna™, a potential first-in-class personalized T-cell therapy for patients suffering from multiple sclerosis. [Opexa Therapeutics, Inc.] Press Release

Vilcek Prize for Biomedical Science Split between Two Giants of Immunology
The Vilcek Foundation is pleased to name Richard A. Flavell and Ruslan Medzhitov as the co-winners of the 2013 Vilcek Prize for Biomedical Science. Drs. Flavell and Medzhitov, both professors at Yale University School of Medicine and investigators with the Howard Hughes Medical Institute, were selected for their research that elucidated the fundamental roles of the innate immune system. [The Vilcek Foundation]
Press Release

POLICY NEWS

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)

EVENTS

NEW Controversies in Rheumatology & Autoimmunity – CORA
April 4-6, 2013
Budapest, Hungary

NEW Keystone Symposia on Molecular and Cellular Biology: Advances in the Knowledge and Treatment of Autoimmunity
April 4-9, 2013
Whistler, Canada

NEW Stem Cells & Cell Therapy Summit
September 5-6, 2013
London, United Kingdom

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

JOB OPPORTUNITIES

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

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)

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


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)


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