Immune Regulation News Volume 9.01 | Jan 13 2017

TOP STORY

A TLR7 Agonist Enhances the Antitumor Efficacy of Obinutuzumab in Murine Lymphoma Models via NK Cells and CD4 T Cells

Investigators demonstrated, in syngeneic human CD20-expressing models of lymphoma, that systemic administration of a Toll-like receptor 7 (TLR7) agonist increases responses when administered in combination with obinutuzumab and protects against disease recurrence. [Leukemia] Full Article

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K48-Linked KLF4 Ubiquitination by E3 Ligase Mule Controls T-Cell Proliferation and Cell Cycle Progression

Scientists report that Lys-48-linked ubiquitination of the transcription factor KLF4 mediated by the E3 ligase Mule promotes T-cell entry into S phase. [Nat Commun] Full Article

The Microbiota Maintain Homeostasis of Liver-Resident γδT-17 Cells in a Lipid Antigen/CD1d-Dependent Manner

Researchers showed hepatic γδT cells are liver-resident cells and predominant producers of IL-17A. The microbiota sustain hepatic IL-17A-producing γδ T (γδT-17) cell homeostasis, including activation, survival and proliferation. [Nat Commun] Full Article

Chronic Innate Immune Activation of TBK1 Suppresses mTORC1 Activity and Dysregulates Cellular Metabolism

The authors genetically separated inflammatory and metabolic phenotypes by showing that Sting deficiency rescued both inflammatory and metabolic phenotypes, whereas Irf3 deficiency only rescued inflammation on the Trex1^−/− background, and many metabolic defects persist in Trex1^−/−Irf3^−/− cells and mice. [Proc Natl Acad Sci USA] Abstract

Lacrimal Gland–Derived IL-22 Regulates IL-17-Mediated Ocular Mucosal Inflammation

Using a cross-sectional patient study and a well-characterized murine model of dry eye disease (DED), the authors investigated the immunoregulatory function of interleukin-22 (IL-22) in the pathogenesis of DED. [Mucosal Immunol] Abstract

RNY (YRNA)-Derived Small RNAs Regulate Cell Death and Inflammation in Monocytes/Macrophages

Scientists studied the role of RNY-derived small RNAs (s-RNYs) in human and mouse monocytes/macrophages and have shown that in lipid-laden monocytes/macrophages s-RNY expression is timely correlated to the activation of both NF-κB and caspase 3-dependent cell death pathways. [Cell Death Dis] Full Article

IK Acts as an Immunoregulator of Inflammatory Arthritis by Suppressing T_H17 Cell Differentiation and Macrophage Activation

Investigators showed that in transgenic mice expressing truncated IK cytokine, inflammatory arthritis symptoms were ameliorated as the result of suppression of the differentiation of T_H1 and T_H17 cells and of macrophage activation. [Sci Rep] Full Article

Weissella cibaria WIKIM28 Ameliorates Atopic Dermatitis-Like Skin Lesions by Inducing Tolerogenic Dendritic Cells and Regulatory T Cells in BALB/c Mice

The intake of W. cibaria WIKIM28 increased the proportion of CD4⁺CD25⁺Foxp3⁺ regulatory T cells in mesenteric lymph nodes (MLNs) and IL-10 levels in polyclonally stimulated MLN cells. [Sci Rep] Full Article

CD24 Aggravates Acute Liver Injury in Autoimmune Hepatitis by Promoting IFN-γ Production by CD4⁺ T Cells

Decreased interferon-γ (IFN-γ) production by hepatic CD4⁺ T cells in CD24-deficient mice was detected, which was correlated with downregulated phosphorylation of STAT1 in hepatic tissue. In vitro experiments also supported the conclusion that CD24 deficiency impaired IFN-γ production by CD4⁺ T cells following concanavalin A, CD3/CD28 and phorbol myristate acetate/ionomycin stimulation. [Cell Mol Immunol] Full Article

TCR Signaling and CD28/CTLA-4 Signaling Cooperatively Modulate T Regulatory Cell Homeostasis

Scientists examined the differential effects of CD28 and CTLA-4 interaction with CD80/CD86, as well as MHC class II–TCR interaction within mouse T regulatory cell (Treg) pools and CD4⁺ and CD8⁺ T cell pools. Blockade of CD80/CD86 with CTLA-4–Ig markedly reduced the cycling and absolute numbers of memory phenotype (MP) Tregs and MP CD4⁺ T cells, with minimal effect on the naive phenotype T cell subpopulations. [J Immunol] Abstract

PI3Kγ Deficient NOD-Mice Are Protected from Diabetes by Restoring the Balance of Regulatory to Effector-T-Cells

PI3Kγ-deficiency promoted regulatory-T-cell generation in-vitro and in-vivo. Furthermore, PI3Kγ-inhibitor inhibited proliferation and cytokine production of a human CD4⁺ T-cell clone specific for GAD555-567 peptide that was isolated from a patient with type 1 diabetes. [PLoS One] Full Article

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An Expanding Stage for Commensal Microbes in Host Immune Regulation

The authors discuss the major components of the microbial community in the gut and how its members collectively and individually exert regulatory roles in the host immune system and lymphoid structure development, as well as the functions of several major immune cell types. [Cell Mol Immunol] Abstract

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Sanofi and ImmuNext Enter into Agreement to Develop Treatments for Autoimmune Diseases

Sanofi and ImmuNext, Inc., announced an agreement focused on the development of a novel antibody with the potential to treat a range of autoimmune diseases including lupus and multiple sclerosis. [sanofi-aventis U.S. LLC.] Press Release

Kite Pharma and Fosun Pharma Establish Joint Venture in China to Develop and Commercialize Autologous T-Cell Therapies to Treat Cancer

Kite Pharma and Shanghai Fosun Pharmaceutical (Group) Co., Ltd., announced a joint venture, Fosun Pharma Kite Biotechnology Co., Ltd., to develop, manufacture and commercialize axicabtagene ciloleucel in China with the option to include additional products, including two T cell receptor product candidates from Kite. [Kite Pharma, Inc.] Press Release

TG Therapeutics Announces Completion of Enrollment and B-Cell Depletion Data from Part 1 of Ongoing Phase II Multiple Sclerosis Study

TG Therapeutics, Inc. announced the completion of enrollment into Part 1 of its ongoing Phase II study of TG-1101, the company’s novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis. [TG Therapeutics, Inc.] Press Release

TG Therapeutics Announces Orphan Drug Designation for the Combination of TG-1101 and TGR-1202 for Treatment of Chronic Lymphocytic Leukemia

TG Therapeutics, Inc. announced that the U.S. Food and Drug Administration has granted orphan drug designation covering the combination of TG-1101, the company’s novel, glycoengineered anti-CD20 monoclonal antibody, and TGR-1202 the company’s oral, next generation PI3K delta inhibitor, for the treatment of patients with chronic lymphocytic leukemia. [TG Therapeutics, Inc.] Press Release

This Year’s Crafoord Prize Is Awarded for Fundamental Discoveries in Immune Regulation

Three immunology researchers share 2017’s Crafoord Prize in Polyarthritis, for which the prize money is 6 million Swedish krona. The research being rewarded deals with the discovery of regulatory T cells, cells that can be regarded as our immune system’s security guards. [The Crafoord Prize (PR Newswire Association LLC.)] Press Release

Gates Foundation Research Can’t Be Published in Top Journals

One of the world’s most influential global health charities says that the research it funds cannot currently be published in several leading journals, because the journals do not comply with its open-access policy. [Nature News] Editorial

White House Announces Review Process for Risky Virus Studies

Federal officials released a plan to help U.S. agencies decide whether to fund controversial studies that make viruses more dangerous. The guidance may finally bring an end to a moratorium that has kept a handful of experiments funded by the Department of Health and Human Services on hold for more than two years. [ScienceInsider] Editorial

US Energy Agency Strengthens Protections for Scientists

The US Department of Energy has released new guidelines to protect researchers from political interference — a move that many say is long overdue. [Nature News] Editorial

NEW Keystone Symposium, Immune Regulation in Autoimmunity and Cancer
March 26-30, 2017
Whistler, United States

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NEW Postdoctoral Fellow – Immunology (Institute of Molecular and Cell Biology)

NEW PhD Position – Cell Signaling, Gene Regulation and Quantitative Biology (Hebrew University of Jerusalem)

NEW Scientist Positions – Immunology (New York Blood Center)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Senior Scientist (Immatics Biotechnologies GmbH)

Postdoctoral Position – Vascular Control of Immune Cell Infiltration and Metastasis (German Cancer Research Center)

Senior Scientist – Immunology (Immusoft Corporation)

Postdoctoral Position – Immunology of HIV-1 and Cancer (University of Alabama at Birmingham)

Postdoctoral Position – Visceral Pain and Neuro-Immune Interaction (KU Leuven)

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

Postdoctoral Fellow – Molecular Immunology (University of California, San Diego)

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