Immune Regulation News Volume 8.40 | Oct 28 2016

TOP STORY

Epigenetic Stability of Exhausted T Cells Limits Durability of Reinvigoration by PD-1 Blockade

Blocking PD-1 can re-invigorate exhausted CD8 T cells (T_EX) and improve control of chronic infections and cancer. However, whether blocking PD-1 can reprogram T_EX into durable memory T cells is unclear. Researchers found that re-invigoration of T_EX in mice by PD-L1 blockade caused minimal memory development. [Science] Abstract | Press Release

(Ranked by impact factor of the journal)

Immunomodulatory Functions of BTLA and HVEM Govern Induction of Extrathymic Regulatory T Cells and Tolerance by Dendritic Cells

Investigators report that efficient induction of regulatory T (Treg) cells was instructed by BTLA⁺DEC205⁺CD8⁺CD11c⁺ dendritic cells (DCs) and the immunomodulatory functions of BTLA. In contrast, T cell activation in steady state by total CD11c⁺ DCs that include a majority of DCs that do not express BTLA did not induce Treg cells and had no lasting impact on subsequent immune responses. [Immunity] Abstract | Press Release | Graphical Abstract

Dendritic Cells Regulate Extrafollicular Autoreactive B Cells via T Cells Expressing Fas and Fas Ligand

Researchers used two conventional dendritic cell (cDC) depletion systems to investigate the role of cDCs on a classical Toll-like receptor-dependent autoreactive extrafollicular (EF) response elicited in rheumatoid-factor B cells by DNA-containing immune complexes. Contrary to their hypothesis, cDC depletion amplified rather than dampened the EF response in Fas-intact but not Fas-deficient mice. [Immunity] Abstract | Graphical Abstract

RASGRP1 Deficiency Causes Immunodeficiency with Impaired Cytoskeletal Dynamics

In a patient with recurrent bacterial and viral infections, born to healthy consanguineous parents, scientists used homozygosity mapping and exome sequencing to identify a biallelic stop-gain variant in RASGRP1. This variant segregated perfectly with the disease and has not been reported in genetic databases. [Nat Immunol] Abstract

Programs for the Persistence, Vigilance and Control of Human CD8⁺ Lung-Resident Memory T Cells

Tissue-resident memory T cells (T_RM cells) in the airways mediate protection against respiratory infection. Scientists characterized T_RM cells expressing integrin α_E that reside within the epithelial barrier of human lungs. [Nat Immunol] Abstract

CD4⁺ Foxp3⁺ T Cells Promote Aberrant IgG Production and Maintain CD8⁺ T Cell Suppression during Chronic Liver Disease

Elevated CD4⁺ Foxp3⁺ T cells were evident in both human liver disease and a mouse model of chemically induced liver injury despite marked activation and spontaneous IgG production by intrahepatic B cells. While this population suppressed CD8⁺ T cell responses, aberrant B cell activities were maintained due to expression of CD40L on a subset of CD4⁺ Foxp3⁺ T cells. [Hepatology] Abstract

Inflammatory Cues Enhance TGFβ Activation by Distinct Subsets of Human Intestinal Dendritic Cells via Integrin αvβ8

Researchers showed that a key activator of TGFβ, integrin αvβ8, is highly expressed on human intestinal dendritic cells (DCs), specifically on the CD1c⁺ but not the CD141⁺ intestinal DC subset. Expression was significantly upregulated in intestinal DC from inflammatory bowel disease patients, indicating that inflammatory signals may upregulate expression of this key TGFβ-activating molecule. [Mucosal Immunol] Full Article

Block of Both TGF-β and IL-2 Signaling Impedes Neurophilin-1⁺ Regulatory T Cell and Follicular Regulatory T Cell Development

The authors investigated the interacting roles of TGF-β and IL-2 on the function regulatory T cells. They took advantage of dnTGF-βRII Il2ra^−/− mouse model, which allows a direct mechanistic approach to define the relative roles of TGF-β and IL-2 on Treg development. [Cell Death Dis] Full Article

Pulmonary α-1,3-Glucan–Specific IgA-Secreting B Cells Suppress the Development of Cockroach Allergy

Investigators determined that an Ab to microbial α-1,3-glucan binds an Enterobacter species and cockroach allergen. Neonatal, but not adult, mice immunized with this α-1,3-glucan–bearing Enterobacter are protected against cockroach allergy. [J Immunol] Abstract | Press Release

Interferon-Driven Deletion of Antiviral B Cells at the Onset of Chronic Infection

Using adoptive transfer experiments in the context of a chronic lymphocytic choriomeningitis virus infection of mice, the authors documented rapid depletion of virus-specific B cells that coincided with the early type I interferon (IFN-I) response to infection. They found that the loss of activated B cells was driven by IFN-I signaling to several cell types including dendritic cells, T cells, and myeloid cells. [Sci Immunol] Abstract | Press Release

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Nociceptor Sensory Neuron–Immune Interactions in Pain and Inflammation

The dialog between nociceptor neurons and the immune system is a fundamental aspect of inflammation, both acute and chronic. A better understanding of these interactions could produce approaches to treat chronic pain and inflammatory diseases. [Trends Immunol] Abstract

Dendritic Cells and Cancer Immunity

Bypassing suppressive pathways or directly activating dendritic cells (DCs) can unleash a T-cell response, and although clinical efficacy has proven elusive, therapeutic targeting of DCs continues to hold translational potential in combinatorial approaches. [Trends Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation research field.

Janssen Partners with University of Pennsylvania and Castleman Disease Collaborative Network to Launch First Global Patient Registry for Castleman Disease

Janssen Research & Development, LLC announced the launch of ACCELERATE, a first-of-its-kind, patient-driven natural history registry dedicated to empowering patients with Castleman Disease to contribute their own personal medical information to advance the knowledge of the disease, including its diagnosis and treatment. [Janssen Research & Development, LLC] Press Release

aTyr Pharma Receives FDA Fast Track Designation for Resolaris™ to Treat Facioscapulohumeral Muscular Dystrophy (FSHD)

aTyr Pharma, Inc. announced that its product candidate Resolaris^™ was granted Fast Track designation by the US Food and Drug Administration (FDA) for the treatment of facioscapulohumeral muscular dystrophy, making it the first known therapeutic candidate for the treatment of FSHD to receive the designation. [aTyr Pharma, Inc.] Press Release

Topline Results from Two-Year Follow-Up Study of Viaskin Peanut Show Long-Lasting and High Levels of Desensitization to Peanut

DBV Technologies announced topline results from the two-year OLFUS-VIPES study supporting the durable effect and favorable safety profile of Viaskin Peanut for the treatment of peanut-allergic children. OLFUS-VIPES, or OLFUS, is an open-label, follow-up study to VIPES, the company’s Phase IIb clinical trial of Viaskin Peanut. [DBV Technologies] Press Release

Opsona Therapeutics Ltd. Receives Orphan Designation for Myelodysplastic Syndrome with OPN-305, a First-in-Class Monoclonal Antibody that Blocks Toll-Like Receptor 2

Opsona Therapeutics Ltd. announced that it has received orphan drug designation from United States Food and Drug Administration for myelodysplastic syndromes. OPN-305 is a novel proprietary humanized IgG4 monoclonal antibody against Toll-Like Receptor 2, a key target within the innate immune system. [Opsona Therapeutics Ltd.] Press Release

Scientific Challenges Loom for Canada’s Popular Prime Minister

Many in Canada’s science community say they are reserving judgement, waiting to see whether Trudeau can sustain his string of victories as he tackles some of country’s thorniest science-policy issues. [Nature News] Editorial

Review Finds Misconduct in Events Surrounding WHO Fetal Growth Study

For the first time in its 68-year history, the World Health Organization (WHO) has concluded that researchers are guilty of research misconduct. An independent review commissioned by WHO has found that “research ethics misconduct occurred” in a multimillion-dollar global study on fetal growth led by researchers at the University of Oxford in the United Kingdom. [ScienceInsider] Editorial

Two Major California Research Institutes Will Merge

One of the biggest nonprofit biomedical research outfits in the world is getting a new translational medicine research arm, aimed at speeding the conversion of basic research insights into novel medicines. Officials at the Scripps Research Institute announced that it will merge with the California Institute for Biomedical Research, which was launched in 2012 as a nonprofit version of a drug development company. [ScienceInsider] Editorial

To Save Money, NSF Requires University Cost-Sharing for Rotators

The National Science Foundation (NSF) has decided that universities should pay 10% of the salaries of faculty members working temporarily at the agency. NSF hopes the new policy will demonstrate its commitment to saving taxpayer dollars without alienating the academic community that it relies upon to stay on the cutting edge of basic science. [ScienceInsider] Editorial

NEW Keystone Symposium: Asthma: From Pathway Biology to Precision Therapeutics
February 12-16, 2017
Keystone, United States

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NEW MRC WIMM Prize PhD Studentships – Various Projects (University of Oxford)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Senior/Advanced Research Assistant – CRISPR/Cas9 Screens in Immune Cells (Wellcome Trust Sanger Institute)

Scientist – T Cells in Autoimmune Diabetes (Helmholtz Zentrum Munchen)

Postdoctoral Position – Mucosal Immunology/Neuro-Immune Interaction (KU Leuven)

Postdoctoral Position – Immunology (Klinikum der Universität München)

Faculty Positions – Immunology (Ohio State University)

Faculty Position – Immunogen Development and Evaluation (Fred Hutchinson Cancer Research Center)

Research Associate – Cellular Therapy (California Institute for Biomedical Research)

Director – Immunobiology and Microbial Pathogenesis (The Salk Institute for Biological Studies)

Assistant Associate or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Immunology (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Molecular Immunology (University of California, San Diego)

Postdoctoral Fellow Position – Stem Cell Biology & Immunology (Toronto General Research Institute & McEwen Centre for Regenerative Medicine)

Faculty Position – Immunology (Vanderbilt University Medical Center)

Postdoctoral Fellow – Mucosal Immunology (University of Utah)

Postdoctoral Research Scientist (National Taiwan University)

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