Volume 7.17 | May 15

Immune Regulation News 7.17 May 15, 2015
Immune Regulation News
     In this issue: Publications | Reviews | Science News | Industry News | Policy News | Events | Jobs
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TOP STORY
A Trigger that Likely Unleashes Autoimmune Disease
Researchers believe they have discovered a group of cells that trigger autoimmune disease, as well as the molecular ‘trigger guard’ that normally holds them in check. These previously undetected cells are renegade versions of the cells that make the ‘high affinity’ antibodies required for long-term immunity. [Press release from Garvan Institute discussing online prepublication in Immunity] Press Release | Abstract | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Melanoma-Intrinsic β-Catenin Signaling Prevents Anti-Tumor Immunity
Researchers identified a melanoma-cell-intrinsic oncogenic pathway that contributes to a lack of T-cell infiltration in melanoma. Using autochthonous mouse melanoma models, they identified the mechanism by which tumor-intrinsic active β-catenin signaling results in T-cell exclusion and resistance to anti-PD-L1/anti-CTLA-4 monoclonal antibody therapy. [Nature] Abstract | Press Release

IL-7-Induced Glycerol Transport and TAG Synthesis Promotes Memory CD8+ T Cell Longevity
Scientists discovered that IL-7 induces expression of the glycerol channel aquaporin 9 (AQP9) in virus-specific memory CD8+ T cells, but not naive cells, and that AQP9 is vitally required for their long-term survival. [Cell] Abstract | Graphical Abstract | Video

Differential Fc-Receptor Engagement Drives an Anti-Tumor Vaccinal Effect
Researchers demonstrated that FcγR expression by CD11c+ antigen-presenting cells is required to generate anti-tumor T cell responses upon FcγR-mediated cytotoxicity-mediated tumor clearance. [Cell]
Abstract | Graphical Abstract | Press Release

Common Clonal Origin of Central and Resident Memory T Cells following Skin Immunization
Investigators immunized mice through the skin with a protein antigen, a chemical hapten, or a non-replicating poxvirus. For every abundant resident memory T cell clone generated in the skin, an abundant central memory T cell clone bearing the identical T cell receptor was present in the lymph nodes. [Nat Med]
Abstract | Press Release

Integrin αvβ8-Mediated TGF-β Activation by Effector Regulatory T Cells Is Essential for Suppression of T-Cell-Mediated Inflammation
Scientists showed that effector regulatory T (Treg) cells express high amounts of the integrin αvβ8, which enables them to activate latent transforming growth factor-β (TGF-β). Treg-cell-specific deletion of integrin αvβ8 did not result in a spontaneous inflammatory phenotype, suggesting that this pathway is not important in Treg-cell-mediated maintenance of immune homeostasis. [Immunity]
Full Article | Graphical Abstract | Press Release

The Autoimmunity-Associated Gene CLEC16A Modulates Thymic Epithelial Cell Autophagy and Alters T Cell Selection
Investigators generated Clec16a knock-down mice in the nonobese diabetic model for type 1 diabetes and found that Clec16a silencing protected against autoimmunity. Disease protection was attributable to T cell hyporeactivity, which was secondary to changes in thymic epithelial cell stimuli that drive thymocyte selection. [Immunity] Abstract | Graphical Abstract | Press Release

Microbe-Dependent Lymphatic Migration of Neutrophils Modulates Lymphocyte Proliferation in Lymph Nodes
Scientist established a photoconversion-based system to monitor the fate of neutrophils recruited to inflamed skin. While neutrophils are efficiently recruited to sites of both microbial and sterile lesions, subsequent re-localization to draining lymph nodes happens only when bacteria are present in the primary lesion. [Nat Commun] Full Article | Press Release

Type I Interferons Regulate Eomesodermin Expression and the Development of Unconventional Memory CD8+ T Cells
Researchers show that type I interferon signaling in CD8+ T cells directly activates eomesodermin gene expression. Consistent with this observation, the phenotype, function and age-dependent expansion of ‘virtual memory’ CD8+ T cells are strongly affected in absence of type I interferon signaling. [Nat Commun]
Full Article | Press Release

Immune-Checkpoint Proteins VISTA and PD-1 Nonredundantly Regulate Murine T-Cell Responses
To determine whether V-domain immunoglobulin suppressor of T-cell activation (VISTA) synergizes with another immune-checkpoint, programmed death 1 (PD-1), investigators characterized the immune responses in VISTA-deficient, PD-1-deficient (KO) mice and VISTA/PD-1 double KO mice. [Proc Natl Acad Sci USA] Abstract

Function and Regulation of Self-Reactive Marginal Zone B Cells in Autoimmune Arthritis
Researchers explored the influence of self-reactive innate B cells in the development of collagen-induced arthritis, a mouse model of rheumatoid arthritis. They showed that splenic marginal zone, but not B-1 B cells exhibit spontaneous IgM reactivity to autologous collagen II in naïve mice. [Cell Mol Immunol] Abstract

Free Extracellular miRNA Functionally Targets Cells by Transfecting Exosomes from Their Companion Cells
The authors describe that extracellular miR-150, extracted from exosomes, is still able to mediate antigen-specific suppression. They determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of effector T cells, which resulted in antigen-specific suppression of their function. [PLoS One] Full Article | Press Release

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REVIEWS
Cancer Stem Cells and Tumor-Associated Macrophages: A Roadmap for Multitargeting Strategies
Investigators summarize the recent molecular data concerning the multilayered relationship between cancer stem cells and tumor-associated macrophages that form a key component of the tumor microenvironment. They also discuss the therapeutic implications of targeting this synergistic interplay. [Oncogene] Abstract

The Role of Nuclear Receptors in Regulation of Th17/Treg Biology and Its Implications for Diseases
The authors focus on the most recent discoveries concerning the roles of nuclear receptors in regulating the T helper 17 (Th17)/regulatory T (Treg) cell-fate determination. [Cell Mol Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation research field.
 
SCIENCE NEWS
Novel Immunomodulatory Treatment Induces Apoptosis in Melanoma
Histogen, Inc. presented new research on its 105F immunomodulatory treatment candidate for melanoma. After treatment with 105F, melanoma cells were shown to release interleukin 6 and TNF-α. [Press release from Histogen, Inc. discussing research presented at the 2015 Society of Investigative Dermatology (SID) Annual Meeting, Atlanta] Press Release

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INDUSTRY NEWS
Lilly and Sanford-Burnham Announce Collaboration to Investigate Immunological Therapies
Eli Lilly and Company and Sanford-Burnham Medical Research Institute will investigate potential therapeutics using biotechnology approaches in targeting multiple immune checkpoint modulators for the treatment of immunological diseases such as lupus, Sjögren’s Syndrome, inflammatory bowel disease and other autoimmune disorders. [Eli Lilly and Company] Press Release

Sanofi Exercises Option on Second Therapeutic Program with Selecta Biosciences to Develop an Antigen-Specific Immunotherapy Based on Synthetic Vaccine Particle Technology
Selecta Biosciences, Inc. announced that, under the terms of an existing strategic global collaboration, Sanofi has exercised its option to an exclusive license to develop an immunotherapy for the treatment of celiac disease. [Selecta Biosciences, Inc.] 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 12th World Congress on Inflammation
August 8-12, 2015
Boston, United States

Visit our events page to see a complete list of events in the immune regulation community.
 
JOB OPPORTUNITIES
NEW Process Facilitator (Opexa Therapeutics)

NEW Postdoctoral Fellow – Immune Tolerance (Stanford University)

Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Autoimmunity and Antibody Engineering (Karolinska Institutet)

Project Leader – Immunology (Cellectis Inc.)

Postdoctoral Fellow – Immunology (Boston Children’s Hospital)

Postdoctoral Fellow – Genomic and Immunogenomic Aspects of Lymphomas (University of Chicago)

Principal Scientist – Antibody Discovery, Biologics Research (Janssen Research & Development LLC.)

Postdoctoral Fellow – Immunopathogenesis of Multiple Sclerosis (University of Iowa)

Senior Scientist – Immunology (National Institute of Immunology)

Assistant Professor – Immunology (Northwestern University)


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