Immune Regulation News Volume 12.13 | Apr 17 2020

TOP STORY

Bacterial Metabolism of Bile Acids Promotes Generation of Peripheral Regulatory T Cells

Researchers screened the major species of deconjugated bile acids for their ability to potentiate the differentiation of periphery Treg cells. They found that the secondary bile acid 3β-hydroxydeoxycholic acid increased Foxp3 induction by acting on dendritic cells (DCs) to diminish their immunostimulatory properties. [Nature] Abstract | Press Release

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Dendritic Cell-Derived Hepcidin Sequesters Iron from the Microbiota to Promote Mucosal Healing

The authors identified conventional dendritic cells (cDCs) as a source of hepcidin that was induced by microbial stimulation in mice, prominent in the inflamed intestine of humans, and essential for tissue repair. cDC-derived hepcidin acted on ferroportin-expressing phagocytes to promote local iron sequestration, which regulated the microbiota and consequently facilitated intestinal repair. [Science] Abstract

Early Fate Defines Microglia and Non-Parenchymal Brain Macrophage Development

Investigators identified two phenotypically, transcriptionally, and locally distinct brain macrophages throughout development, giving rise to either microglia or border-associated macrophages. Two macrophage populations were already present in the yolk sac suggesting an early segregation. [Cell] Abstract | Graphical Abstract

Lipid-Droplet Formation Drives Pathogenic Group 2 Innate Lymphoid Cells in Airway Inflammation

Scientists showed that tissue-resident type 2 ILCs (ILC2s) displayed a distinct metabolic signature upon chronic activation. In the context of allergen-driven airway inflammation, ILC2s increased their uptake of both external lipids and glucose. [Immunity] Abstract

CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity

CXCR1 and CXCR2 agonists proved to be the major mediators of cancer-promoted neutrophil extracellular trap (NET)osis. NETs wrapped and coated tumor cells and shielded them from cytotoxicity, as mediated by CD8⁺ T cells and natural killer (NK) cells, by obstructing contact between immune cells and the surrounding target cells. [Immunity] Abstract | Graphical Abstract

Interleukin 17 and Senescent Cells Regulate the Foreign Body Response to Synthetic Material Implants in Mice and Humans

The authors found increased numbers of IL17-producing γδ⁺ T cells and CD4⁺ T helper 17 cells as well as senescent stromal cells in the fibrotic capsules. Analysis in a murine model demonstrated an early innate IL17 response to implanted synthetic material particles that was mediated by innate lymphoid cells and γδ⁺ T cells. [Sci Transl Med] Abstract | Press Release

The Neonatal Microenvironment Programs Innate γδ T Cells through the Transcription Factor STAT5

Investigators showed that γδT17 cells rapidly proliferated within neonatal lymph nodes and gut, where, upon entry, they upregulated T-bet and coexpressed IL-17, IL-22, and IFN-γ in a STAT3- and retinoic acid-dependent manner. Neonatal expansion was halted in mice conditionally deficient in STAT5, and its loss resulted in γδT17 cell depletion from all adult organs. [J Clin Invest] Full Article | Graphical Abstract

Genome-Wide Analysis Highlights Contribution of Immune System Pathways to the Genetic Architecture of Asthma

Bioinformatics analyses prioritized candidate causal genes at 52 loci, including CD52, and demonstrated that asthma-associated variants were enriched in regions of open chromatin in immune cells. Researchers showed that a murine anti-CD52 antibody mimicked the immune cell-depleting effects of a clinically used human anti-CD52 antibody and reduced allergen-induced airway hyperreactivity in mice. [Nat Commun] Abstract

Natural Killer Cells Modulate Motor Neuron-Immune Cell Cross Talk in Models of Amyotrophic Lateral Sclerosis

Using a mouse model of familial-ALS, hSOD1G93A, investigators demonstrated NK cell accumulation in the motor cortex and spinal cord, with an early CCL2-dependent peak. NK cell depletion reduced the pace of MN degeneration, delayed motor impairment and increases survival. [Nat Commun] Full Article

Enterovirus A71 Oncolysis of Malignant Gliomas

In mice with implanted subcutaneous gliomas, intraneoplastic inoculation of EV-A71 caused significant tumor growth inhibition. In mice bearing intracranial orthotopic gliomas, intraneoplastic inoculation of EV-A71 substantially prolonged survival. [Mol Ther] Abstract | Graphical Abstract

Ligand-Mediated Targeting of Cytokine Interleukin-27 Enhances Its Bioactivity In Vivo

Scientists describe the effects of targeted IL-27 gene delivery on prostate cancer cells in vitro and in vivo and how the targeting enhances bioactivity of the IL-27 cytokine. They applied the IL-27 gene delivery protocol utilizing sonoporation with the goal of reducing prostate tumor growth in an immunocompetent TC2R C57/BL6 model. [Mol Ther Methods Clin Dev] Abstract | Full Article

Collagen-Binding IL-12 Enhances Tumor Inflammation and Drives the Complete Remission of Established Immunologically Cold Mouse Tumors

Researchers showed that, after intravenous administration of a collagen-binding domain (CBD) fused to IL-12 in mice bearing aggressive mouse tumors, CBD-IL-12 accumulated in the tumor stroma due to exposed collagen in the disordered tumor vasculature. [Nat Biomed Eng] Abstract

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Modulation of Regulatory T Cell Function and Stability by Co-Inhibitory Receptors

The authors summarized recent data regarding the role of co-inhibitory molecules in the control of T_reg cell function and stability, with a focus on their roles and potential therapeutic use in autoimmunity and cancer. [Nat Rev Immunol] Abstract

The Genetics of Macrophage Activation Syndrome

Macrophage activation syndrome (MAS), or secondary hemophagocytic lymphohistiocytosis (HLH), is a cytokine storm syndrome associated with multi-organ system dysfunction and high mortality rates. Laboratory and clinical features resemble primary HLH, which arises in infancy from homozygous mutations in various genes critical to the perforin-mediated cytolytic pathway employed by NK cells and cytotoxic CD8 T lymphocytes. [Genes Immun] Abstract

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Intensity Therapeutics Signs Clinical Collaboration Agreement with Bristol Myers Squibb for Advanced Solid Tumors

Intensity Therapeutics announced it has entered into a clinical trial collaboration agreement with Bristol Myers Squibb Company. The program will evaluate the safety and efficacy of Intensity’s lead product INT230-6, an investigational, novel and potent anti-cancer drug designed to directly kill cancer cells through intratumoral injection and improve immune cell recognition of cancer, when dosed in combination with Bristol Myers Squibb’s Cytotoxic T Lymphocyte-Associated Antigen 4 immune checkpoint inhibitor Yervoy^® [Intensity Therapeutics] Press Release

Phase III Clinical Trial of Tedopi^® OSE Immunotherapeutics Announces Positive Top-Line Results for Step-1 of Its Trial ‘Atalante 1’ in Non-Small Cell Lung Cancer

OSE Immunotherapeutics announced that the primary endpoint was met in the predefined Step-1 analysis of its Phase III clinical trial of investigational product Tedopi^®, called Atalante 1, in HLA-A2 positive non-small cell lung cancer patients after failure from immune checkpoint inhibitors [OSE Immunotherapeutics] Press Release

Aldeyra Announces Positive Top-Line Phase I Clinical Trial Results and Clinical Development Plans for ADX-629

Aldeyra Therapeutics, Inc. announced positive top-line Phase I clinical trial results for ADX-629, a first-in-class orally available reactive aldehyde species inhibitor in development for the treatment of systemic immune-mediated diseases. [Aldeyra Therapeutics, Inc.] Press Release

How Research Funders Are Tackling Coronavirus Disruption

While science is crucial to the fight against COVID-19, researchers confined to their homes and unable to carry on with grant-funded work are becoming increasingly concerned about how the coronavirus pandemic will affect their funding. [Nature News] Editorial

WHO’s Tedros, Expressing ‘Regret’ over Trump Move to Cut Funding, Says His Focus Is on ‘Saving Lives’

The head of the World Health Organization expressed “regret” that President Trump intends to cut off US funding to the agency over its handling of the coronavirus, but pointedly avoided criticizing the US move. [STAT News] Editorial

Ending Coronavirus Lockdowns Will Be a Dangerous Process of Trial and Error

After the novel coronavirus made its way from China around the world, one country after another adopted harsh measures to stop SARS-CoV-2 from spreading and overwhelming hospitals. They have hit the pause button on their economies and their citizens’ lives, stopping sports events, religious services, and other social gatherings. [ScienceInsider] Editorial

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NEW Postdoctoral Researcher – Cancer Treatment Sensitivty (Johannes Kepler University of Linz)

NEW Chair – Department of Microbiology and Immunology (Western University)

Postdoctoral Fellow – Acute Myeloid Leukemia (Icahn School of Medicine at MOunt Sinai)

Senior Scientist – Immunotherapy and Transplant Rejection (Regensburg Center for Interventional Immunology)

Postdoctoral Researcher – Intestinal Tissue Regeneration (Karolinska Institutet)

Principle Scientist – Cancer and Auto-Immune Disorders (Sanofi)

Postdoctoral Fellow – Mucosal Immunology and Allergies (University of Michigan)

Assistant Professor – Pharmacology and Cancer Biology (Wayne State University)

Postdoctoral Fellow – Leukemia Biology and Dendritic Cells (Dana Farber Cancer Institute)

Postdoctoral Fellowships – Immunology (University of Oslo)

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