Immune Regulation News Volume 8.41 | Nov 4 2016

TOP STORY

Deleting an Nr4a1 Super-Enhancer Subdomain Ablates Ly6C^low Monocytes while Preserving Macrophage Gene Function

Combining ChIP-seq and molecular approaches scientists identified a single, conserved, sub-domain within the Nr4a1 enhancer that was essential for Ly6C^low monocyte development. Mice lacking this enhancer lacked Ly6C^low monocytes but retained Nr4a1 gene expression in macrophages during steady state and in response to LPS. [Immunity] Abstract | Graphical Abstract | Press Release

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Neutrophils License iNKT Cells to Regulate Self-Reactive Mouse B Cell Responses

Scientists identified an accumulation of B cell–helper neutrophils in the spleen that interacted with innate-type invariant natural killer T cells (iNKT cells) to regulate B cell responses. They found that neutrophil-dependent expression of the death-receptor ligand FasL by iNKT cells was needed to restrict autoantibody production. [Nat Immunol] Abstract | Press Release

Fibroblastic Reticular Cells Regulate Intestinal Inflammation via IL-15-Mediated Control of Group 1 ILCs

Researchers found that production of the cytokine IL-15 by fibroblastic reticular cells was essential for the maintenance of group 1 innate lymphoid cells (ILCs) in Peyer’s patches and mesenteric lymph nodes. [Nat Immunol] Abstract

Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus

Using single-cell transcriptional profiling, investigators uncover a unique signature of Granzyme B⁺ CD4⁺ cytotoxic T cells, which distinguishes them from other CD4⁺ T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T cell signature. [Cell Rep] Full Article | Graphical Abstract

Rescue of Tolerant CD8⁺ T Cells during Cancer Immunotherapy with IL2:Antibody Complexes

The authors found that interleukin-2 cytokine/antibody complex (IL2c) treatment rescued tumor-specific CD8⁺ T cells from a state of established tolerance, providing effective immunotherapy in tumor-bearing mice. Expression of the transcription factor T-bet was necessary to drive intratumoral IFNγ production and effector activity by T cells rescued with IL2c. [Cancer Immunol Res] Abstract

Eosinophils Are Required to Suppress Th2 Responses in Peyer’s Patches during Intestinal Infection by Nematodes

The authors infected eosinophil-deficient ΔdblGATA-1 mice with the type 2 helper T (Th2)-inducing small intestinal nematode Heligmosomoides polygyrus and found that parasite fecundity was decreased in the absence of eosinophils. A lack of eosinophils resulted in significantly augmented expression of GATA-3 and IL-4 by CD4⁺ T cells during acute infection, a finding strictly limited to Peyer’s patches. [Mucosal Immunol] Abstract

Pollen/TLR4 Innate Immunity Signaling Initiates IL-33/ST2/Th2 Pathways in Allergic Inflammation

In experimental allergic conjunctivitis induced by short ragweed pollen, typical allergic signs, stimulated IL-33/ST2 signaling and overproduced Th2 cytokine were observed in ocular surface, cervical lymph nodes and isolated CD4⁺ T cells of BALB/c mice. [Sci Rep] Full Article

Surface-Bound Bovine Serum Albumin Carrier Protein as Present in Recombinant Cytokine Preparations Amplifies T Helper 17 Cell Polarization

The authors investigated T helper 17 lineage (TH₁₇) amplification by coating of cytokine preparations. Cytokine preparations coated to the surface compared to the same amount given in solution significantly enhanced TH₁₇ polarization assessed by flow cytometry and interleukin (IL)-17A, IL-17F and RORγt mRNA expression. [Sci Rep] Full Article

Lin28b Regulates Fetal Regulatory T Cell Differentiation through Modulation of TGF-β Signaling

Increased fetal regulatory T cell (Treg) differentiation is mediated by the RNA-binding protein Lin28b, which is overexpressed in fetal T cells as compared with adult cells. When Lin28b expression is decreased in naive fetal T cells, they exhibit decreased Treg differentiation that is associated with decreased TGF-β signaling and lowered expression of TGF-βRI, TGF-βRIII, and SMAD2. [J Immunol] Abstract

Immunoregulatory Effects of 4-(4-Chlorophenyl)-1-(5-Amino-3-Methylisoxazole-4-Carbonyl)-Thiosemicarbazide (06K) in Non-Immunized and SRBC-Immunized Mice

Immunoregulatory properties of 06K derivative (4-(4-chlorophenyl)-1-(5-amino-3-methylisoxazole-4-carbonyl)-thiosemicarbazide) in mouse in vivo models were investigated. Several in vivo models were used: humoral and cellular immune response, carrageenan inflammatory reaction and determination of lymphocyte subsets in non-immunized mice. [J Pharm Pharmacol] Abstract

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PD-1–PD-L1 Immune-Checkpoint Blockade in B-Cell Lymphomas

The authors focus on the role of programmed cell-death protein 1/programmed cell death 1 ligand 1 (PD-1–PD-L1) blockade in unleashing host antitumor immune responses against various B-cell lymphomas, and summarize the clinical studies of this approach performed to date. [Nat Rev Clin Oncol] Abstract

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Targovax Reports Promising Early Data on Vaccine Now in Mesothelioma Clinical Trial

Targovax presented preclinical and clinical results of the anti-tumor efficacy of its cancer vaccine ONCOS-102 for the treatment of malignant mesothelioma. [Press release from Targovax (BioNews Services, LLC) discussing research presented at the Changing the Face of Modern Medicine: Stem Cells & Gene Therapy Symposium, Florence] Press Release

Roswell Park Gets FDA Approval for Clinical Study of Cuban Lung Cancer Vaccine, License for Joint U.S.–Cuba Commercial Partnership

Gov. Andrew Cuomo announced that a partnership formed during his historic New York State Trade Mission to Cuba last year has resulted in a milestone of international collaboration: the launch of a U.S. clinical trial of a Cuban immunotherapy developed by the Center of Molecular Immunology for lung cancer. [Roswell Park Cancer Institute] Press Release

DNAtrix Announces First Patients Treated in Phase II Trial with DNX-2401 and KEYTRUDA

DNAtrix announced that the first patients have been treated in a multicenter Phase II trial investigating its oncolytic adenovirus, DNX-2401, in combination with KEYTRUDA^®, Merck’s anti-PD-1 therapy, in patients with recurrent glioblastoma. [DNAtrix] Press Release

TapImmune Announces Commercialization Pathway for Its HER2neu Vaccine

TapImmune, Inc. provided an update on the progression of a HER2neu vaccine into clinical trials. [TapImmune, Inc.] Press Release

Omeros Files Orphan Drug Application for OMS721 in Immunoglobulin A Nephropathy

Omeros Corporation announced that it has filed an application for orphan drug designation with the U.S. Food and Drug Administration for OMS721 in the treatment of immunoglobulin A nephropathy. [Omeros Corporation] Press Release

Russian Science at the Crossroads

As the United States goes to the polls after an unprecedentedly vulgar election campaign, its former cold-war rival is exuding strength and confidence. Just last week, Russia cited its proud history of exploration and science in Antarctica when giving the green light to an international agreement to create a vast marine reserve in the Ross Sea. [Nature News] Editorial

Publisher Pulls 58 Articles by Iranian Scientists over Authorship Manipulation

A tranche of 58 articles authored by 282 Iran-based researchers were retracted by a leading scientific publisher, which said it had found signs that the peer review and publication processes had been compromized. [Nature News] Editorial

Young Scientists Ditch Postdocs for Biotech Start-Ups

There is a vanguard of young biomedical scientists who have started companies instead of taking the conventional academic path and pursuing postdoctoral studies after their PhDs. Among the factors driving this change are an infusion of money into early-stage biotech investing, the emergence of biotech incubators and the scarcity of academic jobs in science. [Nature News] Editorial

Beyond Trump vs Clinton: A Scientist’s Guide to the US Election

Choices that voters make will influence other levels of government — and some of these decisions will steer the course of science and science policy. [Nature News] Editorial

Tracker Flags Up Failures to Report Clinical Trials

An automated tool has trawled through thousands of records on the world’s leading clinical-trials database to reveal which drug firms and academic institutions are failing to publish the results of their trials. The US Department of Health and Human Services announced tougher rules to push the researchers that it funds to publish clinical-trial designs and results. [Nature News] Editorial

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