Immune Regulation News Volume 10.03 | Jan 26 2018

TOP STORY

Innate and Adaptive Lymphocytes Sequentially Shape the Gut Microbiota and Lipid Metabolism

Scientists identified, using advanced multiplex quantitative imaging methods, an extensive and persistent phosphorylated-STAT3 signature in group 3 innate lymphoid cells and intestinal epithelial cells that is induced by IL-23 and IL-22 in mice that lack CD4⁺ T cells. [Nature] Abstract

(Ranked by impact factor of the journal)

Interleukin-10 Directly Inhibits CD8⁺ T Cell Function by Enhancing N-Glycan Branching to Decrease Antigen Sensitivity

Researchers demonstrated that the antigen sensitivity of CD8⁺ T cells was decreased during chronic infection and that this was directly mediated by IL-10. Mechanistically, they showed that IL-10 induced the expression of Mgat5, a glycosyltransferase that enhances N-glycan branching on surface glycoproteins. [Immunity] Abstract | Graphical Abstract

NKp46 Receptor-Mediated Interferon-γ Production by Natural Killer Cells Increases Fibronectin 1 to Alter Tumor Architecture and Control Metastasis

Scientists used reflectance confocal microscopy imaging in humans and in mice to visualize tumor architecture in vivo. They demonstrated that signaling via the natural killer (NK) cell receptor NKp46 (human) and Ncr1 (mouse) induced interferon-γ secretion from intratumoral NK cells. [Immunity] Full Article | Graphical Abstract

Selective Autophagy of the Adaptor TRIF Regulates Innate Inflammatory Signaling

The authors found that loss of the autophagy-related gene Atg16l1 promoted accumulation of the adaptor TRIF and downstream signaling in macrophages. Multiplex proteomic profiling identified SQSTM1 and Tax1BP1 as selective autophagy-related receptors that mediated the turnover of TRIF. [Nat Immunol] Abstract

Intestinal IFN-γ-Producing Tr1-Cells Co-Express CCR5 and PD-1, and Down-Regulate IL-10 in the Inflamed Gut of IBD Patients

Researchers identified and characterized human intestinal type-1 regulatory (Tr1-) cells, and investigated if they are a relevant cellular source of IL-10 in inflammatory bowel diseases (IBDs). Intestinal Tr1-cells could be identified by the co-expression of CCR5 and PD-1 in humans and mice. [J Allergy Clin Immunol] Abstract

T Cells Specific for Post-Translational Modifications Escape Intrathymic Tolerance Induction

Investigators showed a mouse model of autoimmunity in which disease development is dependent on post-translational modification (PTM) of the tissue-restricted self-antigen collagen type II. PTM-reactive T cells escape thymic selection, though the PTM variant constitutes the dominant form in the periphery. [Nat Commun] Full Article

Leptin Receptor q223r Polymorphism Influences Neutrophil Mobilization after Clostridium difficile Infection

In a murine model of C. difficile infection, the authors demonstrated that mice homozygous for the same single nucleotide polymorphism have more blood and tissue leukocytes (specifically neutrophils), exaggerated tissue inflammation, and higher mortality as compared with control mice, despite similar pathogen burden. [Mucosal Immunol] Abstract

Cambogin Suppresses Dextran Sulphate Sodium-Induced Colitis by Enhancing Treg Cell Stability and Function

Researchers investigated the effect of cambogin in a mouse model of dextran sulphate sodium-induced colitis and whether cambogin attenuates inflammation via Treg-cell-mediated immune modulation. Cambogin up-regulated Treg cell numbers in both the spleen and mesenteric lymph nodes. Furthermore, cambogin prevented Foxp3 loss in human primary Treg cells in vitro. [Br J Pharmacol] Abstract | Full Article

An In Vitro System of Autologous Lymphocytes Culture that Allows the Study of Homeostatic Proliferation Mechanisms in Human Naive CD4 T-Cells

Investigators designed an in vitro culture of human T-cells exposed to rIL7 and autologous antigen-presenting cells that allowed the simultaneous characterization of the different types of homeostatic proliferation. Different subsets of Tregs were generated during homeostatic proliferation in their model. [Lab Invest] Abstract

PD-L1 Reverses Depigmentation in Pmel-1 Vitiligo Mice by Increasing the Abundance of Tregs in the Skin

To determine whether programmed cell death 1 ligand 1 (PD-L1) is a therapy target in vitiligo treatment, Pmel-1 vitiligo mice were treated with a PD-L1 fusion protein. Mechanistically, enrichment of Tregs in the skin was detected after PD-L1 fusion protein treatment in Pmel-1 mice. [Sci Rep] Full Article

High Self-Reactivity Drives T-Bet and Potentiates Treg Function in Tissue-Specific Autoimmunity

Scientists observed that T-bet expression in Tregs, necessary for control of Th1 autoimmunity, could be induced in an IFNγ-independent fashion and, unlike in conventional T cells, was strongly correlated with the strength of T cell receptor signaling. [JCI Insight] Full Article

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Epigenetics, Microbiota, and Intraocular Inflammation: New Paradigms of Immune Regulation in the Eye

The authors discuss how epigenetic mechanisms and microbiota may cooperate to initiate and perpetuate ocular inflammation. [Prog Retin Eye Res] Full Article

Bacterial Pathogenesis and Interleukin-17: Interconnecting Mechanisms of Immune Regulation, Host Genetics, and Microbial Virulence that Influence Severity of Infection

Scientists analyze IL-17/IL-23 signaling in bacterial infection, and examine the interconnecting mechanisms that link immune regulation, host genetics, and microbial virulence in the context of bacterial pathogenesis. [Crit Rev Microbiol] Abstract

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BioLineRx Announces Partial Monotherapy Results from Phase IIa COMBAT Study in Pancreatic Cancer

BioLineRx Ltd. announced partial results from the monotherapy portion of BL-8040’s Phase IIa COMBAT study showing that BL-8040 increases infiltration of T cells into the tumor in patients with metastatic pancreatic cancer. [Press release from BioLineRx Ltd. discussing research presented at the 2018 American Society of Clinical Oncology (ASCO)-Gastrointestinal (GI) Cancers Symposium, San Francisco] Press Release

Alligator Bioscience Contracts Theradex Oncology as Clinical CRO for the Upcoming ATOR-1015 Phase I Study

Alligator Bioscience announced that it has appointed Theradex Oncology, a global contract research organization (CRO) with extensive expertise in oncology clinical development, as CRO for the planned Phase I study of ATOR-1015 for the treatment of metastatic cancer. [Alligator Bioscience AB] Press Release

OSE Immunotherapeutics Receives Notice of Allowance for New Patent by U.S. Patent and Trademark Office that Further Strengthens Intellectual Property Portfolio around Tedopi^® in Immuno-Oncology Applications

OSE Immunotherapeutics announced that it has received a notice of allowance from the U.S. Patent and Trademark Office for a new patent that further expands the company’s intellectual property portfolio around Tedopi^®, a combination of neoepitopes optimized to induce specific T activation in immuno-oncology. [OSE Immunotherapeutics] Press Release

U.S. Scientists Breathe a Sigh of Relief as Government Shutdown to End

It’s over—at least for the moment. The U.S. Senate voted 81–18 to advance legislation funding government activities, essentially ending a partial government shutdown that had moved into its third day. The House of Representatives is expected to follow suit, sending the bill to President Donald Trump for his signature. [ScienceInsider] Editorial

German Scientists Hope for Windfall from Incoming Government

Research budget could rise to 3.5% of gross domestic product if agreement struck during coalition talks holds. [Nature News] Editorial

Nobel Laureate Suggests He Could Fall on Sword over Colleague’s Bogus Paper

Shinya Yamanaka, who won a share of the 2012 Noble Prize in Physiology or Medicine for the discovery of induced pluripotent stem (iPS) cells, has suggested he could resign as director of Kyoto University’s Center for iPS Cell Research and Application in Japan over a fraudulent paper published by center researchers. [ScienceInsider] Editorial

Gender Bias Goes Away When Grant Reviewers Focus on the Science

But female scientists suffer when their research proposals are judged primarily on the strength of their CVs. [Nature News] Editorial

NEW Gordon Research Conferences: Tissue Niches and Resident Stem Cells in Adult Epithelia
August 19-24, 2018
Waterville Valley, New Hampshire, United States

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NEW Postdoctoral Fellow – Myeloid Cells and Type I Interferon Responses (The Wistar Institute)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Laboratory Head – In Vivo Pharmacology (Boehringer Ingelheim)

PhD Positions – Immunology (Regensburg Center for Interventional Immunology)

Postdoctoral Fellow – Regulation of Platelet Mediated Complications (NYU School of Medicine)

Postdoctoral Researcher – Human Microbiome-Immune System Interactions (University of Luxembourg)

Research Scientist – Cellular and Translational Immunology (University of Virginia)

Postdoctoral Scholar – Immunology (Pennsylvania State University)

Postdoctoral Positions – Innate Immunity (University of Connecticut)

Postdoctoral Research Fellow – Inflammation and Immuno-Oncology (Yale School of Medicine)

Postdoctoral Training Opportunity – Infection and Immunity (Institut Pasteur of Shanghai – Chinese Academy of Sciences)

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

Research Fellow Position – Immunology Research (ShanghaiTech University)

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