Immune Regulation News Volume 9.28 | Jul 28 2017

TOP STORY

D-Mannose Induces Regulatory T Cells and Suppresses Immunopathology

Scientists showed that supraphysiological levels of D-mannose safely achievable by drinking-water supplementation suppressed immunopathology in mouse models of autoimmune diabetes and airway inflammation, and increased the proportion of Foxp3⁺ T_reg cells in mice. [Nat Med] Abstract

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Hepatocyte-Derived Exosomes Promote T Follicular Regulatory Cell Expansion during HCV Infection

The authors examined the accumulation of T follicular regulatory (Tfr) cells in the liver compartment during chronic hepatitis C virus (HCV) infection and defined the cellular and molecular mechanisms underlying their expansion. Their analysis revealed a substantial population of Tfr cells in the livers of chronic HCV patients that was absent in liver tissues from non-viral hepatitis or healthy subjects. [Hepatology] Abstract

Cells with Treg-Specific FOXP3 Demethylation but Low CD25 Are Prevalent in Autoimmunity

Investigators found, in comparison with healthy donors, that the frequency of FOXP3⁺ cells within CD127^lowCD25^low CD4⁺ T cells was increased in patients affected by autoimmune disease of varying severity, from combined immunodeficiency with active autoimmunity, systemic lupus erythematosus to type 1 diabetes. [J Autoimmun] Full Article

PKC-Θ Is Dispensable for OX40L-Induced TCR-Independent Treg Proliferation but Contributes by Enabling IL-2 Production from Effector T-Cells

Using CD4⁺ T cells from WT and OX40^−/− mice, researchers established that OX40 mediated activation of NF-kB was critical for Treg proliferation. Although CD4⁺ T cells from PKC-Θ^−/− mice were also defective in GM-CSF derived bone marrow dendritic cell induced Treg proliferation ex vivo, this defect could be readily corrected by adding exogenous IL-2 to the co-cultures. [Sci Rep] Full Article

Curcumin Converts Foxp3⁺ Regulatory T Cells to T Helper 1 Cells in Patients with Lung Cancer

Scientists treated a group of lung cancer (LC) patients with curcumin. The peripheral Tregs and T helper (Th) 1 cells were analyzed by flow cytometry. The results showed that the frequency of peripheral Tregs were markedly higher in LC patients than that in healthy subjects, which was suppressed after treating with curcumin for two weeks. [J Cell Biochem] Abstract

Single and Combined Effect of Retinoic Acid and Rapamycin Modulate the Generation, Activity and Homing Potential of Induced Human Regulatory T Cells

Investigators evaluated the effects of all-trans retinoic acid and rapamycin on the number, phenotype, homing markers expression, DNA methylation, and function of induced human Treg cells in short-term cultures. [PLoS One] Full Article

CBirTox Is a Selective Antigen-Specific Agonist of the Treg-IgA-Microbiota Homeostatic Pathway

The authors generated a fusion protein, CBirTox, comprised of a portion of the carboxy terminus of CBir1, a microbiota flagellin, genetically coupled to cholera toxin B subunit via the A2 linker of cholera toxin. Both dendritic cells and B cells pulsed with CBirTox selectively induced functional CD4⁺Foxp3⁺ Tregs in vitro, and CBirTox augmented CD4⁺Foxp3⁺ cell numbers in vivo. [PLoS One] Full Article

Therapy with Omeprazole Modulates Regulatory T Cell/T Helper 17 Immune Response in Children with Duodenal Ulcers

Researchers determined the effect of omeprazole on the Treg and T helper 17 (Th17)-mediated response in patients with duodenal ulcers (DUs). DU patients were randomly divided into omeprazole and colloid bismuth subcitrate treatment groups. The results showed that DU patients had an imbalanced Treg/Th17 response, as reflected by the higher IL-17 level and Th17 ratio and lower IL-10 level and Treg proportion in serum compared with those in the healthy volunteers. [Inflammopharmacology] Abstract

Clonal Analysis of Regulatory T Cell Defect in Patients with Autoimmune Polyendocrine Syndrome Type 1 Suggests Intrathymic Impairment

Scientists used T cell receptor sequencing to analyze the clonal relationship of major CD4⁺ T cell subsets in three patients and three healthy controls. The naive regulatory T cells showed little overlap with helper T cell subsets, supporting divergence in the thymus. The activated/memory regulatory T cell subset displayed more sharing with helper T cells, but was mainly recruited from the naive regulatory T cell population. [Scand J Immunol] Abstract

Regulatory T-Cell Distribution within Lung Compartments in COPD

The authors used lung tissues from 21 never-smokers without lung disease, 22 current and/or ex-smokers without lung disease (NOS) and 13 current and/or ex-smokers with chronic obstructive pulmonary disease (COPD) for histological analysis. They observed increased T, B, IL-17 and BAFF⁺ cells in small and large airways of COPD individuals; however, in the NOS, they only observed an increase in T and IL-17⁺ cells in small airways. [COPD] Abstract

Helicobacter Species Are Potent Drivers of Colonic T Cell Responses in Homeostasis and Inflammation

Researchers analyzed bacterial-reactive T cell receptor (TCR) transgenic cells and TCR repertoires in a murine colitis model. They found that mucosal-associated Helicobacter species triggered both T_reg cell responses during homeostasis and effector T (T_eff) cell responses during colitis, as suggested by an increased overlap between the T_eff/T_reg TCR repertoires with colitis. [Sci Immunol] Full Article

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New Insights into Blimp-1 in T Lymphocytes: A Divergent Regulator of Cell Destiny and Effector Function

The authors discuss the emerging roles of B lymphocyte-induced maturation protein-1 (Blimp-1) in the complex regulation of gene networks that regulate the destiny and effector function of T cells and provide a Blimp-1-dominated transcriptional framework for T lymphocyte homeostasis. [J Biomed Sci] Full Article

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Lilly and Nektar Therapeutics Announce Alliance to Develop and Commercialize NKTR-358, a Novel Autoimmune Therapy

Eli Lilly and Company and Nektar Therapeutics announced a strategic collaboration to co-develop NKTR-358, a novel immunological therapy discovered by Nektar. NKTR-358, which achieved first human dose in Phase I clinical development in March of 2017, has the potential to treat a number of autoimmune and other chronic inflammatory conditions. [Eli Lilly and Company] Press Release

Kadmon Announces Supplemental Interim Phase II Data of KD025 in Chronic Graft-versus-Host Disease

Kadmon Holdings, Inc. announced supplemental clinical data from the first cohort of an ongoing Phase II clinical trial of the company’s lead Rho-associated coiled-coil kinase 2 inhibitor, KD025, for chronic graft-versus-host disease. [Kadmon Holdings, Inc.] Press Release

Incyte Announces First Patient Treated in Phase III Clinical Trial of Itacitinib for Acute Graft-versus-Host Disease

Incyte Corporation announced that the first patient has been treated in GRAVITAS-301, a pivotal Phase III trial for the first-line treatment of patients with acute graft-versus-host disease (GvHD). The trial will evaluate the efficacy and safety of itacitinib, Incyte’s novel, potent, and selective JAK1 inhibitor, in combination with corticosteroids compared to placebo plus corticosteroids in patients with acute GvHD. [Incyte Corporation] Press Release

GSK Receives FDA Approval for a New Self-Injectable Formulation of Benlysta (Belimumab) for Systemic Lupus Erythematosus

GlaxoSmithKline plc (GSK) announced that the US FDA has approved a new subcutaneous formulation of Benlysta for the treatment of adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy. The approval marks the first subcutaneous self-injection treatment option for patients with SLE. [GlaxoSmithKline plc] Press Release

First Human Embryos Edited in U.S.

The first known attempt at creating genetically modified human embryos in the United States has been carried out by a team of researchers in Portland, Oregon. The effort, led by Shoukhrat Mitalipov of Oregon Health and Science University, involved changing the DNA of a large number of one-cell embryos with the gene-editing technique CRISPR, according to people familiar with the scientific results. [MIT Technology Review] Editorial

Budding UK Innovation Agency Gains Cash — and Clout

UK scientists fearful for their research funds ahead of Brexit were cheered when the government announced it would plough an extra £4.7 billion (US$6.1 billion) into research and development by 2020–21. But the biggest winner from the largely industry-focused cash may be a government innovation agency that is rapidly gaining clout. [Nature News] Editorial

Ding, Ding, Ding! CRISPR Patent Fight Enters Next Round

The University of California has fired another legal salvo in the prolonged patent battle over CRISPR, the revolutionary gene-editing technology that has spawned a billion dollar industry. [ScienceInsider] Editorial

Senate Spending Panel Would Squeeze Science Agencies but Exceed Trump Request

A Senate spending panel voted to reduce funding in 2018 below current levels for several science agencies under its jurisdiction. [ScienceInsider] Editorial

NEW Stem Cell Society Singapore’s (SCSS) Symposium 2017
November 16-17, 2017
Singapore, Singapore

NEW Keystone Symposia: Lymphocytes and Their Roles in Cancer
February 11-15, 2018
Keystone, Colorado, United States

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

NEW 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)

Postdoctoral Fellow – Immunology (Oxford University)

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)

Scientist – Neuroinflammation (University Health Network)

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

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