Immune Regulation News Volume 9.30 | Aug 11 2017

TOP STORY

Study Reveals How to Reprogram Cells in Our Immune System

Scientists revealed a method to reprogram specific T cells. More precisely, they discovered how to turn pro-inflammatory cells that boost the immune system into anti-inflammatory cells that suppress it, and vice versa. [Press release from the Gladstone Institutes discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

Genome-Wide DNA-Methylation Landscape Defines Specialization of Regulatory T Cells in Tissues

Researchers found that epigenetic modifications define the molecular characteristics of tissue T_reg cells. Tagmentation-based whole-genome bisulfite sequencing revealed more than 11,000 regions that were methylated differentially in pairwise comparisons of tissue T_reg cell populations and lymphoid T cells. [Nat Immunol] Abstract

Metabolic and Immune Effects of Immunotherapy with Proinsulin Peptide in Human New-Onset Type 1 Diabetes

Investigators studied safety and mechanistic effects of injecting human leukocyte antigen–DR4(DRB1*0401)–restricted immunodominant proinsulin peptide intradermally every two or four weeks for six months in newly diagnosed type 1 diabetes patients. [Sci Transl Med] Full Article | Press Release

Melatonin Reduces Inflammatory Response in Peripheral T Helper Lymphocytes from Relapsing-Remitting Multiple Sclerosis Patients

The authors evaluated the effects of the in vitro administration of melatonin to peripheral blood mononuclear cells from 64 relapsing-remitting multiple sclerosis patients and 64 sex- and age-matched healthy subjects on T helper (Th) 1, Th9, Th17, Th22 and Treg responses and analyzed the expression of the melatonin effector/receptor system in these cells. [J Pineal Res] Abstract

Tissue-Specific Control of Latent CMV Reactivation by Regulatory T Cells

Researchers investigated the role of Tregs in a mouse model of latent cytomegalovirus (CMV) infection using Foxp3-diphtheria toxin receptor mice. Administration of diphtheria toxin after establishment of latency efficiently depleted Tregs and drove a significant increase in the numbers of functional murine CMV-specific CD4⁺ and CD8⁺ T cells. [PLoS Pathog] Full Article

Regulatory T-Cells from Pancreatic Lymphnodes of Patients with Type-1 Diabetes Express Increased Levels of MicroRNA miR-125a-5p that Limits CCR2 Expression

The authors investigated the microRNA expression profile in Treg cells isolated from peripheral blood and from pancreatic draining lymph nodes (PLN) of type 1 diabetes (T1D) patients and non-diabetic subjects. Among 72 microRNAs analyzed, miR-125a-5p resulted specifically hyper-expressed in Treg cells purified from PLN of T1D patients. [Sci Rep] Full Article

C-C Chemokine Receptor Type 5 (CCR5)-Mediated Docking of Transferred Tregs Protects against Early Blood-Brain Barrier Disruption after Stroke

Scientists determined the role of CCR5 in mediating the docking and activation of transferred Tregs in their protection of early blood-brain barrier disruption after stroke. Adoptive transfer of CCR5^−/− Tregs failed to reduce brain infarct or neurological deficits, indicating an indispensable role of CCR5 in Treg-afforded protection against cerebral ischemia. [J Am Heart Assoc] Full Article

Notch Balances Th17 and Induced Regulatory T Cell Functions in Dendritic Cells by Regulating Aldh1a2 Expression

Investigators demonstrated that dendritic cells (DCs) in mice that are Rbpj deficient in CD11c⁺ cells promoted the differentiation of IL-17A–producing Th17 cells. Those DCs exhibited a reduced ability for differentiating regulatory T cells induced by TGF-β. [J Immunol] Abstract

Lamtor1 Is Critically Required for CD4⁺ T Cell Proliferation and Regulatory T Cell Suppressive Function

The authors showed that Lamtor1-deficient CD4⁺ T cells exhibited marked reductions in proliferation, IL-2 production, mechanistic target of rapamycin complex 1 activity, and expression of purine- and lipid-synthesis genes. Lamtor1-deficient regulatory T cells survived ex vivo as long as wild-type regulatory T cells; however, they exhibited a marked loss of suppressive function and expression of signature molecules, such as CTLA-4. [J Immunol] Abstract

Low Doses of Cholera Toxin and Its Mediator cAMP Induce CTLA-2 Secretion by Dendritic Cells to Enhance Regulatory T Cell Conversion

Scientists found that murine bone marrow-derived dendritic cells treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT or with cAMP, a known mediator CT signals. All three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β). [PLoS One] Full Article

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The Yin and Yang of Regulatory T Cell and Therapy Progress in Autoimmune Disease

The authors summarize the progress and discuss the phenotypic, numeric and functional abnormalities of Tregs and systematically review the progress of Tregs therapy in autoimmune diseases. [Autoimmun Rev] Abstract

Regulatory T Cell Dysfunction in Type 1 Diabetes: What’s Broken and How Can We Fix It?

Researchers highlight the evidence suggesting that a reduction in the functional capacity of different Treg populations contributes to disease development in type 1 diabetes. They also address current controversies regarding the putative causes of this defect and discuss strategies to correct it as a means to reduce or prevent islet destruction in a clinical setting. [Diabetologia] Full Article

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Theravance Biopharma Reports Encouraging Data from First Cohort of Patients in Phase Ib Clinical Trial of TD-1473 in Ulcerative Colitis

Theravance Biopharma, Inc. announced early evidence of localized target engagement from the company’s ongoing Phase Ib clinical trial of TD-1473 in patients with moderate to severe active ulcerative colitis. [Theravance Biopharma, Inc.] Press Release

InDex Pharmaceuticals Receives Orphan-Drug Designation for Pediatric Ulcerative Colitis in the US

InDex Pharmaceuticals Holding AB announced that the FDA has granted orphan-drug designation for the drug candidate cobitolimod for treatment of ulcerative colitis in pediatric patients. [InDex Pharmaceuticals Holding AB] Press Release

Ocugen Receives FDA Orphan Drug Designation for OCU300 (Brimonidine Tartrate) for the Treatment of Ocular Graft versus Host Disease

Ocugen, Inc. announced the FDA has granted orphan drug designation for OCU300 for the treatment of ocular graft versus host disease. [Ocugen, Inc.] Press Release

Americans Are Becoming More Open to Human Genome Editing, Survey Finds, but Concerns Remain

Earlier surveys of Americans found a reluctance to support human genome editing, with many respondents expressing ethical and other concerns about such intentional tinkering. A new survey found that two-thirds of the 1600 respondents thought genome editing was generally “acceptable.” But that acceptance was qualified, and colored by religious beliefs and scientific knowledge. [ScienceInsider] Editorial

Thousands across India March in Support of Science

Thousands of scientists, university students and science enthusiasts gathered in dozens of Indian cities to march in support of science — lamenting their country’s low levels of funding for research, and complaining about government promotion of ‘unscientific ideas’. [Nature News] Editorial

FDA Cracks Down on Pioneering Doctor Who Created a Three-Parent Baby

The New York-based doctor who helped a couple have a child using DNA from three people has been told by the FDA that he can’t go ahead with clinical trials meant to test the technique. [MIT Technology Review] Editorial

CRISPR Patent Battle in Europe Takes a ‘Wild’ Twist with Surprising Player

MilliporeSigma, a subsidiary of pharmaceutical giant Merck KGaA of Darmstadt, Germany, has become a new major player in the complicated European patent battles over CRISPR, the revolutionary genome-editing tool. [ScienceInsider] Editorial

NEW EACR: A Matter of Life or Death: From Basic Cell Death Mechanisms to Novel Cancer Treatments
February 1-3, 2018
Amsterdam, Netherlands

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NEW Postdoctoral Scholar – Regulation of Immune Responses (University of Iowa)

NEW Postdoctoral Fellowships – Immune Signaling and Metabolism (St. Jude Children’s Research Hospital)

NEW Postdoctoral Research Assistant – Immune Regulation by Proteolytic Cascades (University of Oxford)

Postdoctoral Scholar – Tumor Immunology (Washington University School of Medicine)

Postdoctoral Position – Mucosal Immunology (Sainte-Justine Hospital Research Center)

Research Fellow Position – Immunology Research (ShanghaiTech University)

Mouse Scientist – T Cell-Based Therapy (Tessa Therapeutics Pte Ltd.)

Postdoctoral Researcher – Tumor Immunology and Cancer Immunotherapy (University of California, Los Angeles)

Postdoctoral Fellow – Allergy and Immunology (New York University Medical Center)

Postdoctoral Fellow – Neuroimmunology (Duke University)

Postdoctoral Research Fellow – Cancer Immunotherapy (Fred Hutchinson Cancer Research Center)

Principal Senior Scientist – Human Disease Immune Profiling/Precision Immunology (Sanofi)

Postdoctoral Fellow – Cell Biology and Innate Immunity (The Laboratory for Molecular Infection Medicine Sweden)

Postdoctoral Fellow – Inflammatory Bowel Disease (Harvard Medical School)

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

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