Immune Regulation News Volume 10.02 | Jan 19 2018

TOP STORY

NIH Scientists Find Microbes on the Skin of Mice Promote Tissue Healing, Immunity

Beneficial bacteria on the skin of lab mice work with the animals’ immune systems to defend against disease-causing microbes and accelerate wound healing, according to new research from scientists at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH). [Press release from the National Institutes of Health discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Activation of p53 in Immature Myeloid Precursor Cells Controls Differentiation into Ly6c⁺CD103⁺ Monocytic Antigen-Presenting Cells in Tumors

Investigators showed that during immunotherapy, large numbers of cells expressing CD103 arose in murine tumors via direct differentiation of Ly6c⁺ monocytic precursors. Increasing p53 expression using a p53-agonist drug caused a sustained increase in Ly6c⁺CD103⁺ cells in tumors during immunotherapy, which markedly enhanced the efficacy and duration of response. [Immunity] Abstract | Graphical Abstract

Paracrine Wnt5a-β-Catenin Signaling Triggers a Metabolic Program that Drives Dendritic Cell Tolerization

The authors describe a mechanism by which melanomas establish a site of immune privilege via a paracrine Wnt5a-β-catenin-peroxisome proliferator-activated receptor-γ signaling pathway that drives fatty acid oxidation in dendritic cells by upregulating the expression of the carnitine palmitoyltransferase-1A fatty acid transporter. [Immunity] Abstract | Graphical Abstract

Aged Polymorphonuclear Leukocytes Cause Fibrotic Interstitial Lung Disease in the Absence of Regulation by B Cells

Pulmonary immunity requires tight regulation, as interstitial inflammation can compromise gas exchange and lead to respiratory failure. Researchers found a greater number of aged CD11b^hiL-selectin^loCXCR4⁺ polymorphonuclear leukocytes in lung vasculature than in the peripheral circulation. [Nat Immunol] Abstract

Hypoxia-Inducible Factor-1α Is a Critical Transcription Factor for IL-10-Producing B Cells in Autoimmune Disease

Investigators showed that hypoxia-inducible factor-1α (HIF-1α) contributes to IL-10 production by B cells. HIF-1α regulated IL-10 expression, and HIF-1α-dependent glycolysis facilitated CD1d^hiCD5⁺ B cells expansion. [Nat Commun] Full Article

Regulatory T Cells Trigger Effector T Cell DNA Damage and Senescence Caused by Metabolic Competition

The authors showed that human Treg cells initiate DNA damage in effector T cells caused by metabolic competition during cross-talk, resulting in senescence and functional changes that are molecularly distinct from anergy and exhaustion. [Nat Commun] Full Article

Thymic Stromal Lymphopoietin Drives the Development of IL-13⁺ Th2 Cells

Scientists report that a substantial proportion of naive CD4⁺ T cells in spleen and lymph node express receptors for the epithelium-derived inflammatory cytokine thymic stromal lymphopoietin (TSLP). In vivo, high TSLP levels acted directly on CD4⁺ T cells to induce the development of IL-13-single positive and IL-4⁺IL-13⁺ double-positive populations in lymph node. [Proc Natl Acad Sci USA] Full Article

Heteromeric Interactions Regulate Butyrophilin (BTN) and BTN-Like Molecules Governing γδ T Cell Biology

Researchers showed that BTN3A2 regulates the subcellular localization of BTN3A1, including functionally important associations with the endoplasmic reticulum, and is specifically required for optimal BTN3A1-mediated activation of Vγ9Vδ2⁺ T cells. [Proc Natl Acad Sci USA] Full Article

SGK1 Governs the Reciprocal Development of Th17 and Regulatory T Cells

The authors showed that serum- and glucocorticoid-induced kinase 1 (SGK1) restrains the function of Treg cells and reciprocally regulates development of Th17/Treg balance. SGK1 deficiency lead to protection against autoimmunity and enhanced self-tolerance by promoting Treg cell development and disarming Th17 cells. [Cell Rep] Full Article | Graphical Abstract

Systemic IL-2/Anti-IL-2Ab Complex Combined with Sublingual Immunotherapy Suppresses Experimental Food Allergy in Mice through Induction of Mucosal Regulatory T Cells

Investigators combined sublingual immunotherapy (SLIT) with systemic administration of IL-2 associated with an anti-IL-2 monoclonal antibody (IL-2/anti-IL-2Ab) to reverse the IgE-mediated experimental allergy. Tregs were sorted, characterized and adoptively transferred to naïve mice, which were subsequently sensitized. No allergy was experienced in these mice and they discovered a faster and more efficient tolerance induction with the combined therapy compared with SLIT. [Allergy] Abstract

Immunomodulation by Therapeutic Mesenchymal Stromal Cells (MSC) Is Triggered through Phagocytosis of MSC by Monocytic Cells

Scientists examined immunological mechanisms determining the fate of infused MSC and the immunomodulatory response associated with it. Umbilical cord MSC-primed monocytes induced Foxp3⁺ regulatory T cell formation in mixed lymphocyte reactions. These results demonstrated that infused MSC are rapidly phagocytosed by monocytes, which subsequently migrate from the lungs to other body sites. [Stem Cells] Abstract

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Regulation of the Immune Response by the Aryl Hydrocarbon Receptor

Researchers discuss the role of aryl hydrocarbon receptor (AhR) in the regulation of the immune response in the context of autoimmunity, infection, and cancer, as well as the potential opportunities and challenges of developing AhR-targeted therapeutics. [Immunity] Abstract

Myeloid-Derived Suppressor Cells Coming of Age

Myeloid-derived suppressor cells are a heterogeneous population of cells generated during a large array of pathologic conditions ranging from cancer to obesity. Scientists discuss the origin and nature of these cells; their distinctive features; and their biological roles in cancer, infectious diseases, autoimmunity, obesity and pregnancy. [Nat Immunol] Abstract

Immunomodulatory Nonstructural Proteins of Influenza A Viruses

The authors review various functions of the influenza virus nonstructural proteins NS1, PB1-F2, and PA-X in infected cells and how post-transcriptional modifications of these proteins affect the viral life cycle. [Trends Microbiol] Abstract

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

Txcell Obtains Government Funding to Advance Its Lead CAR-Treg Program

TxCell SA announced it has obtained an interest-free loan from Bpifrance, a French government agency, for the preclinical development of its most advanced CAR-Treg program. [TxCell SA] Press Release

Constellation Pharmaceuticals Announces Initiation of Phase Ib/II Study of CPI-1205

Constellation Pharmaceuticals, Inc. announced it has initiated a Phase Ib/II clinical trial to evaluate CPI-1205, a small-molecule inhibitor of enhancer of zeste homolog 2, combined with checkpoint inhibitor ipilimumab and potentially other cancer immunotherapies. [Constellation Pharmaceuticals, Inc.] Press Release

Broad Institute Takes a Hit in European CRISPR Patent Struggle

A decision from the European Patent Office (EPO) has put the Broad Institute in Cambridge, Massachusetts, on shaky ground with its intellectual property claims to the gene-editing tool CRISPR. EPO revoked a patent granted to the Broad for fundamental aspects of the technology, one of several of its patents facing opposition in Europe. [ScienceInsider] Editorial

Brexit Vote Didn’t Spur Quick Exodus from UK Universities

The number of European Union nationals working as academics at British universities increased slightly in the year that the United Kingdom voted to leave the EU, according to figures published by the Higher Education Statistics Agencyon. [Nature News] Editorial

What a US Government Shutdown Would Mean for Science

The National Institutes of Health would stop processing grants, but astronauts in space would keep working. [Nature News] Editorial

In Trump’s First Year, Science Advice Sees a Marked Decline

Since U.S. President Donald Trump took office, expert panels that provide key federal agencies with science advice have had fewer members and met less often than at any time since 1997, when the government started tracking such numbers, a new analysis concludes. [ScienceInsider] Editorial

NEW The 2^nd Annual European Neoantigen Summit
April 24-26, 2018
Amsterdam, Netherlands

Visit our events page to see a complete list of events in the community.

NEW Laboratory Head – In Vivo Pharmacology (Boehringer Ingelheim)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

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)

Postdoctoral Positions – RNA Regulation of T-Cell Based Cancer Immunology (The University of Texas MD Anderson Cancer Center)

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

Research Fellow Position – Immunology Research (ShanghaiTech University)

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