Volume 5.04 | Feb 1

Immune Regulation News 5.04 February 1, 2013
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
Nr4a Receptors Are Essential for Thymic Regulatory T Cell Development and Immune Homeostasis
Researchers showed that the Nr4a nuclear receptors, which are encoded by immediate-early genes upregulated by T cell antigen receptors stimulation in thymocytes, have essential roles in regulatory T cell (Treg) development. Mice that lacked all Nr4a factors could not produce Treg cells and died early owing to systemic autoimmunity. [Nat Immunol] Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

Human Inflammatory Dendritic Cells Induce Th17 Cell Differentiation
Scientists report that human inflammatory dendritic cells, but not inflammatory macrophages, stimulated autologous memory CD4+ T cells to produce interleukin-17 and induce T helper 17 (Th17) cell differentiation from naive CD4+ T cells through the selective secretion of Th17 cell-polarizing cytokines. [Immunity] Abstract

Mutations in GATA2 Cause Human NK Cell Deficiency with Specific Loss of the CD56bright Subset
The authors report that GATA2 is required for the maturation of human NK cells and the maintenance of the CD56bright pool in the periphery. Defects in GATA2 are a novel cause of profound NK cell dysfunction. [Blood] Abstract

Neurokinin-1 Receptor Agonists Bias Therapeutic Dendritic Cells to Induce Type-1 Immunity by Licensing Host Dendritic Cells to Produce IL-12
Scientists demonstrated that neurokinin-1 receptor-signaling activates therapeutic dendritic cells capable of biasing type-1 immunity by inhibition of IL-10 synthesis and secretion, without affecting their low levels of IL-12 production. [Blood] Abstract

Involvement of Toso in Activation of Monocytes, Macrophages, and Granulocytes
Researchers generated Toso-deficient mice and used them to uncover a critical regulatory function of Toso in innate immune activation. Development of innate immune cells was intact in the absence of Toso, but Toso-deficient neutrophils exhibited more reactive oxygen species production and reduced phagocytosis of pathogens compared with controls. [Proc Natl Acad Sci USA] Abstract

TSG-6 Produced by hMSCs Delays the Onset of Autoimmune Diabetes by Suppressing Th1 Development and Enhancing Tolerogenicity
The authors showed that human mesenchymal stem/stromal cells (hMSCs) and TNF-α-stimulated gene 6 (TSG-6), a protein produced by hMSCs in response to signals from injured tissues, delayed the onset of spontaneous autoimmune diabetes in NOD mice by inhibiting insulitis and augmenting regulatory T cells within the pancreas. [Diabetes] Abstract

In Active Relapsing-Remitting Multiple Sclerosis, Effector T Cell Resistance to Adaptive Tregs Involves Interleukin-6-Mediated Signaling
To determine whether effector T cell (Teff) resistance contributes to failed tolerance in relapsing-remitting multiple sclerosis (RRMS), investigators performed regulatory T cell (Treg) suppression assays with Teff from either RRMS patients not on immunomodulatory therapy or healthy individuals. [Sci Transl Med]
Abstract | Press Release

Thymic Stromal Lymphopoietin Elicits Interleukin-33-Independent Innate Lymphoid Cell Responses to Promote Skin Inflammation
The authors identified a population of skin-resident group 2 innate lymphoid cells (ILCs) present in healthy human skin that are enriched in lesional human skin from atopic dermatitis (AD) patients. Group 2 ILCs were also found in normal murine skin and were critical for the development of inflammation in a murine model of AD-like disease. [Sci Transl Med] AbstractPress Release

Generation of an HIV Resistant T-Cell Line by Targeted “Stacking” of Restriction Factors
Researchers used zinc finger nucleases to insert a cocktail of anti-HIV restriction factors into the CCR5 locus in a T-cell reporter line, knocking out the CCR5 gene in the process. Mirroring the logic of highly active antiretroviral therapy, this strategy provides multiple parallel blocks to infection, dramatically limiting pathways for viral escape, without relying on random integration of transgenes into the genome. [Mol Ther] Abstract | Press Release

TRIF-Mediated TLR3 and TLR4 Signaling Is Negatively Regulated by ADAM15
Toll/IL-1R domain-containing adaptor inducing IFN (TRIF)-interacting partners were identified by immunoprecipitation of the TRIF signaling complex, followed by protein identification using liquid chromatography mass spectrometry. Following stimulation of cells with a TLR3 or TLR4 ligand, the authors identified a disintegrin and metalloprotease 15 (ADAM15) as a novel TRIF-interacting partner. [J Immunol] Abstract

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REVIEWS

Six-of-the-Best: Unique Contributions of γδ T Cells to Immunology
The authors conclude that while B cells and αβ T cells are commonly thought to contribute primarily to the antigen-specific effector and memory phases of immunity, γδ T cells are distinct in that they combine conventional adaptive features (inherent in their T cell receptors and pleiotropic effector functions) with rapid, innate-like responses that can place them in the initiation phase of immune reactions. [Nat Rev Immunol] Abstract

Advances in Targeting Cell Surface Signaling Molecules for Immune Modulation
Advances in the understanding of the human immune system, along with valuable lessons learned from the first generation of therapeutic biologics, are aiding the design of the next generation of immunomodulatory biologics with better therapeutic efficacy, minimized adverse effects and long-lasting clinical benefit. [Nat Rev Drug Discov] Abstract

Negative Regulation of Human Mononuclear Phagocyte Function
This review discusses inhibitory regulation of pattern-recognition receptor-induced macrophage functions and the consequences of dysregulation of these functions and highlights mechanisms that have a role in intestinal macrophages and in human macrophage studies. [Mucosal Immunol] Abstract

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INDUSTRY NEWS

Lupus Research Institute Awards $3.6 Million for Bold Novel Research Driving to New Treatments and a Cure
The Lupus Research Institute awards $3.6 million in Novel Research Grants to allow 12 investigators to pursue ground-breaking studies with potential for transformative results. The $300,000 grants provide scientists with the resources to devote their talent to lupus research for three years. [Lupus Research Institute]
Press Release

BIVIGAM™ [Immune Globulin Intravenous (Human), 10% Liquid] Is the First New IVIG Product Approved with a Validated and FDA Approved Thrombin Generation Assay (TGA) Test

Biotest Pharmaceuticals Corporation announced the U.S. Food and Drug Administration’s (FDA) approval of BIVIGAM™, its new intravenous immune globulin (IVIG), for the treatment of patients with primary humoral immunodeficiency. BIVIGAM is the first new intravenous immune globulin to be approved by the FDA with a validated assay for measuring potential thrombogenic activity. [Biotest Pharmaceuticals Corporation]
Press Release

Generex Points to Potential of Antigen Express Technology Platform beyond Its AE37 Breast Cancer Vaccine
Generex Biotechnology Corporation explained the potential of the technology platform used as the basis for its novel breast cancer immunotherapy product AE37. The main potential advantage cancer immunotherapy like AE37 as compared to other cancer therapies is the ability to direct the body’s immune system against targeted cancer cells, similar to other vaccines that direct the immune system against targeted infections. [Generex Biotechnology Corporation] Press Release


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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 AIMS – Advanced Immunochematology & Molecular Symposium
April 21-22, 2013
Baton Rouge, United States

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)

Postdoctoral Fellow (Medical University of Warsaw)

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)


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