Immune Regulation News Volume 10.23 | Jun 22 2018

TOP STORY

LSD1 Ablation Stimulates Anti-Tumor Immunity and Enables Checkpoint Blockade

Researchers demonstrated that ablation of the histone demethylase LSD1 in cancer cells increases repetitive element expression, including endogenous retroviral elements, and decreases expression of RNA-induced silencing complex components. This lead to double-stranded RNA stress and activation of type 1 interferon, which stimulated anti-tumor T cell immunity and restrained tumor growth. [Cell] Abstract | Graphical Abstract

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Suppression of IL-17F, but Not of IL-17A, Provides Protection against Colitis by Inducing Treg Cells through Modification of the Intestinal Microbiota

The authors found that Il17f^–/– mice resisted chemically induced colitis, but Il17a^–/– mice did not, and that Il17f^–/– CD45RB^hiCD4⁺ T cells induced milder colitis in lymphocyte-deficient Rag2^–/– mice, accompanied by an increase in intestinal Treg cells. [Nat Immunol] Abstract

Microglia Inhibit Photoreceptor Cell Death and Regulate Immune Cell Infiltration in Response to Retinal Detachment

Using the newly identified microglia marker P2ry12 and microglial depletion strategies, they demonstrated that retinal microglia are rapidly activated in response to retinal detachment (RD) and migrated into the injured area within 24 hours post-RD, where they closely associate with infiltrating macrophages, a population distinct from microglia. [Proc Natl Acad Sci USA] Full Article

Cancer-Associated Fibroblasts Affect Intratumoral CD8⁺ and FoxP3⁺ T Cells via Interleukin 6 in the Tumor Microenvironment

The authors investigated whether cancer-associated fibroblasts can regulate tumor-infiltrating lymphocytes and their role in tumor immunosuppression. [Clin Cancer Res] Abstract

T Cell-Directed IL-17 Production by Lung Granular γδ T Cells Is Coordinated by a Novel IL-2 and IL-1β Circuit

Researchers showed a role for IL-2 triggering IL-17 production by lung granular γδ T cells as IL-17 synthesis and neutrophil recruitment was reduced by IL-2 blocking mAbs in vitro and in vivo. [Mucosal Immunol] Abstract

Combination of Asiatic Acid and Naringenin Modulates NK Cell Anticancer Immunity by Rebalancing Smad3/Smad7 Signaling

Scientists report that retrieving the balance between Smad3 and Smad7 signaling with asiatic acid and naringenin effectively inhibited tumor progression in mouse models of invasive melanoma and lung carcinoma by promoting NK cell development and cytotoxicity against cancer. They found that Smad3 physically bound Id2 and IRF2 to suppress NK cell production and NK cell-mediated cytotoxicity against cancer. [Mol Ther] Abstract

Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Activate Quiescent T Cells and Elevate Regulatory T Cell Response via NF-κB in Allergic Rhinitis Patients

Investigators identified the immunomodulatory role of induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) on resting peripheral blood mononuclear cells (PBMCs) from allergic rhinitis patients. PBMCs were cocultured with iPSC-MSCs without any stimulation, following which lymphocyte proliferation, activation of T cells, T_H1/T_H2 and Treg cell differentiation, and Treg cell function were analyzed. [Stem Cell Res Ther] Full Article

CD4⁺ Foxp3⁺ Regulatory T Cell-Mediated Immunomodulation by Anti-Depressants Inhibiting Acid Sphingomyelinase

In vitro stimulation of acid sphingomyelinase (ASM)-deficient T cells in the presence of TGF-β and IL-2 leads to higher numbers of induced Treg cells. Pharmacological inhibition of the ASM with a clinically used tricyclic antidepressant such as amitriptyline in mice or in tissue culture of murine or human T cells induced higher frequencies of Treg cells among CD4⁺ T cells within a few days. [Biol Chem] Abstract

Common Gamma Chain Cytokines Promote Regulatory T Cell Development and Survival at the CD4⁺ CD8⁺ Stage in the Human Thymus

Investigators showed that interleukin‐2 promotes the development of FOXP3⁺ thymocytes and enhances their survival at the double positive (DP) phase. IL‐2 increased the frequency of FOXP3⁺ cells and promoted the Treg phenotype after TCR‐mediated positive selection at the most mature DP stage. [Scand J Immunol] Abstract

Co-Expression of LAG3 and TIM3 Identifies a Potent Treg Population that Suppresses Macrophage Functions in Colorectal Cancer Patients

Compared to controls, colorectal cancer patients presented mild upregulations in CD4⁺CD25^+/hi T cells and in the more canonical CD4⁺CD25^+/hiFoxp3⁺ Treg cells in peripheral blood mononuclear cells. [Clin Exp Pharmacol Physiol] Abstract

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Regulatory T Cells in Autoimmune Disease

The authors summarize the newer concepts of Treg cell instability, Treg cell plasticity and tissue-specific Treg cells, and their relationship to autoimmunity. [Nat Immunol] Abstract

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TxCell: First In Vivo Proof-of-Concept Data with CD8⁺ CAR-Treg Presented

TxCell SA announced that Dr. Carole Guillonneau, PhD, will present proof-of-concept preclinical data, generated by TxCell and CRTI. [Press release from TxCell SA discussing research presented at the 2018 Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS), San Francisco] Press Release

CrownBio Enters Partnership with Pierre Fabre to Accelerate Discovery and Development of Immuno-Oncology Agents

Crown Bioscience announced that it has been selected by Pierre Fabre Research Institute as one of their partners to advance their immuno-oncology drug discovery pipeline. [Crown Bioscience] Press Release

Jeffrey Modell Foundation Awards $3.7 Million for Global Primary Immunodeficiency Research

To date, $3.7 million has been awarded by the Jeffrey Modell Foundation for research into genetic immunodeficiency diseases known as Primary Immunodeficiency. Research programs focus on translational research and support of underserved regions with healthcare disparities, with projects currently being conducted in 32 countries led by 45 leading investigators. [Jeffrey Modell Foundation (PR Newswire Association LLC.)] Press Release

Study into the Causes of Crohn’s Disease Hits Major Milestone

After ten years and a worldwide effort, Crohn’s and Colitis Canada announced that the world-renowned Genetic, Environmental, Microbial (GEM) Project has reached its goal of 5,000 participants. Launched in 2008 at Mount Sinai Hospital in Toronto, the GEM Project is the world’s largest clinical study investigating the causes of Crohn’s disease. [Crohn’s & Colitis Canada] Press Release

White House Proposes a Narrowing of FDA’s Mission — And a New Name

The Trump administration has proposed a fundamental change to the mission of the Food and Drug Administration, one that would transfer most of the responsibility for regulating food safety to the Department of Agriculture and rename the FDA the “Federal Drug Administration.” [STAT News] Editorial

Trump’s Plan to Reshuffle Government Strikes Familiar Notes

President Donald Trump proposed reorganizing parts of the federal government in ways that should sound very familiar to those who follow U.S. science policy. The plan, labeled “Delivering Government Solutions in the 21st Century,” would affect federal research agencies in ways great and small. [ScienceInsider] Editorial

Two University of Rochester Professors Resign in Protest

Celeste Kidd, an associate professor in the University of Rochester’s brain and cognitive sciences department, announced her move to the University of California, Berkeley, earlier this month. Kidd and her husband, Steven Piantadosi—another professor at the university—are leaving in response to the university’s handling of the sexual harassment allegations against brain sciences professor Florian Jaeger. [The Scientist] Editorial

Hundreds of U.S. Scientists Urge More Transparency in Animal Research

Breaking with a history of reticence, nearly 600 scientists, students, and lab animal workers published a letter in USA Today that calls on U.S. research institutions to “embrace openness” about their animal research. [ScienceInsider] Editorial

NEW Infection and Chronic Disease Meeting
July 12, 2018
London, United Kingdom

NEW 47^th Annual Scientific Meeting of the Australasian Society for Immunology
December 2-6, 2018
Perth, Australia

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NEW Postdoctoral Fellowships – Immunometabolism (St. Jude Children’s Research Hospital)

NEW Assistant/Associate Professor – Immunology (University of Massachusetts)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

PhD Student – Cellular Immunotherapy (Glycostem Therapeutics)

Postdoctoral Research Fellow – Human Systems Immunology (University of Oslo)

PhD Position – Characterization of the Immune Pathways that Stimulate Autoimmunity Caused By ADAR1 Deficiency (VIB)

PhD Student Positions – Immunology (Multiple Locations)

Postdoctoral Research Scientist – Immunology (Lilly)

Postdoctoral Fellowship – Immunology (University of South Carolina)

Postdoctoral Position – Tumor Immunology and Cancer Immunotherapy (Vlaams Instituut voor Biotechnologie)

Postdoctoral Fellow – Immunology (Boston University School of Medicine)

Postdoctoral Fellow – Innate Immune Signaling (Houston Methodist Research Institute)

Postdoctoral Associate Position – Tumor Immunology/Immunotherapy (Duke Cancer Institute)

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

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