Immune Regulation News Volume 9.11 | Mar 24 2017

TOP STORY

Exposure to Bacterial CpG DNA Protects from Airway Allergic Inflammation by Expanding Regulatory Lung Interstitial Macrophages

Scientists found that exposure to CpG DNA (CpG) expanded regulatory lung interstitial macrophages (IMs) from monocytes infiltrating the lung or mobilized from the spleen. Trafficking of IM precursors to the lung was independent of CCR2, a chemokine receptor required for monocyte mobilization from the bone marrow. [Immunity] Abstract | Press Release | Graphical Abstract

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Combined Toll-Like Receptor 3/7/9 Deficiency on Host Cells Results in T-Cell-Dependent Control of Tumor Growth

Researchers showed that Toll-like receptor 3, 7 and 9 deficiencies on host cells, after initial tumor growth, result in complete tumor regression and induction of anti-tumor immunity. Tumor regression requires the combined absence of all three receptors, is dependent on both CD4 and CD8 T cells and protects the mice from subsequent tumor challenge. [Nat Commun] Full Article

Suppressive IL-17A⁺Foxp3⁺ and ex-Th17 IL-17A^negFoxp3⁺ T_reg Cells Are a Source of Tumor-Associated T_reg Cells

Scientists showed that Th17 cells are a source of tumor-induced Foxp3⁺ cells. In addition to natural T_reg and induced T_reg cells that develop from naive precursors, suppressive IL-17A⁺Foxp3⁺ and ex-Th17 Foxp3⁺ cells are converted from IL-17A⁺Foxp3^neg cells in tumor-bearing mice. [Nat Commun] Full Article

Activin-A Co-Opts IRF4 and AhR Signaling to Induce Human Regulatory T Cells that Restrain Asthmatic Responses

The authors showed that the cytokine activin-A instructs the generation of CD4⁺ T cells that express the type 1 regulatory T-cell–associated molecules IL-10, inducible T-cell costimulator, lymphocyte activation gene 3 protein, and CD49b, and exert strongly suppressive functions toward allergic responses induced by naive and in vivo-primed human T helper 2 cells. [Proc Natl Acad Sci USA] Abstract

Myocardial Infarction Primes Autoreactive T Cells through Activation of Dendritic Cells

In steady state, cardiac self-antigen α-myosin was presented in the heart-draining mediastinal lymph node (mLN) by conventional dendritic cell (cDC)1s, driving the proliferation of antigen-specific CD4⁺ TCR-M T cells and their differentiation into regulatory cells. Following myocardial infarction, all DC subsets infiltrated the heart, whereas only cDCs migrated to the mLN. [Cell Rep] Full Article | Graphical Abstract

IL-36γ Signaling Controls the Induced Regulatory T Cell–Th9 Cell Balance via NFκB Activation and STAT Transcription Factors

Investigators report that the interleukin-1 (IL-1) family member IL-36γ signals through IL-36 receptor, myeloid differentiation primary response gene 88, and nuclear factor-κBp50 in CD4⁺ T cells to potently inhibit Foxp3-expressing induced regulatory T cell development, while concomitantly promoting the differentiation of T helper (Th)9 cells via a IL-2-STAT5-(signal transducer and activator of transcription factor 5) and IL-4-STAT6-dependent pathway. [Mucosal Immunol] Abstract

BAP31 Is Involved in T Cell Activation through TCR Signal Pathways

Researchers created a BAP31 conditional knockdown mouse by performing a knockdown of BAP31 in the thymus. They demonstrated that the maturation of T cells is normal but the number of T cells is less in the thymus of the knockout mouse. [Sci Rep] Full Article

Priming of Transcriptional Memory Responses via the Chromatin Accessibility Landscape in T Cells

Scientists performed global FAIRE-seq profiling of chromatin accessibility in a human T cell transcriptional memory model. Primary activation induced persistent accessibility changes, and secondary activation induced secondary-specific opening of previously less accessible regions associated with enhanced expression of memory-responsive genes. [Sci Rep] Full Article

Helios Expression and Foxp3 TSDR Methylation of IFNy⁺ and IFNy^– Treg from Kidney Transplant Recipients with Good Long-Term Graft Function

The authors investigated in kidney transplant recipients with good long-term stable graft function the absolute cell counts of IFNy⁺ Treg subsets and whether their expression of Foxp3 is stable or transient. [PLoS One] Full Article

Up-Regulation of LFA-1 Allows Liver-Resident Memory T Cells to Patrol and Remain in the Hepatic Sinusoids

Using intravital imaging, the authors found that CD8⁺ T cell patrolling in the hepatic sinusoids is dependent on LFA-1–intercellular adhesion molecule–1 interactions. Liver-resident CD8⁺ T cells up-regulate LFA-1 compared with effector memory cells, presumably to facilitate this behavior. [Sci Immunol] Abstract | Press Release

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Neutrophils as Protagonists and Targets in Chronic Inflammation

The authors summarize the current understanding of the roles of neutrophils in chronic inflammation, with a focus on how they communicate with other immune and non-immune cells within tissues. [Nat Rev Immunol] Abstract

The Mazy Case of Notch and Immunoregulatory Cells

Scientists discuss the current knowledge about Notch-dependent regulation of generation and function of 2 subsets of the immunoregulatory system, namely regulatory T cells and myeloid-derived suppressor cells. [J Leukoc Biol] Abstract

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OncoSec Medical’s Intratumoral Plasmid IL-12 Demonstrates Effectiveness at Enhancing Tumor Immunogenicity in Preclinical Tumor Models

OncoSec Medical Incorporated presented a poster titled “Intratumoral Electroporation-mediated IL-12 Gene Therapy Can Enhance Tumor Immunogenicity”. [Press release from OncoSec Medical Incorporated discussing research presented at the Keystone Symposia Conference, Cancer Immunology and Immunotherapy: Taking a Place in Mainstream Oncology, Whistler] Press Release | Poster

Kineta RLR Agonist Demonstrates Tumor Regression and an Adaptive Immune Response in Colon Carcinoma Model

Kineta, Inc. announced the discovery and characterization of several “hit to lead” small molecule compounds that activate interferon response factor 3 via RIG-I like receptor pathways and demonstrate immune-mediated tumor regression in a murine colon carcinoma mouse model. [Press release from Kineta, Inc. discussing research presented at the Keystone Symposia Conference, Cancer Immunology and Immunotherapy: Taking a Place in Mainstream Oncology, Whistler] Press Release

NantKwest Announces FDA Grant of Orphan Drug Designation for the Company’s aNK Natural Killer Cell Therapy in Merkel Cell Carcinoma

NantKwest, Inc. announced that the FDA has granted Orphan Drug Designation to the company’s activated natural killer (aNK) cell therapy for treatment of patients with advanced Merkel cell carcinoma. [NantKwest, Inc.] Press Release

FDA Grants Approval for BAVENCIO^® (Avelumab), the First Immunotherapy Approved for Metastatic Merkel Cell Carcinoma

EMD Serono and Pfizer Inc. announced that the US Food and Drug Administration (FDA) has approved BAVENCIO^® Injection 20 mg/mL, for intravenous use, for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma. [EMD Serono] Press Release

BioLineRx Announces Acquisition of Agalimmune Ltd. to Accelerate Expansion of Immuno-Oncology Pipeline

BioLineRx Ltd. announced that it has acquired Agalimmune Ltd., a private UK-based company with an innovative, anti-cancer immunotherapy platform. [BioLineRx Ltd.] Press Release

Gates Foundation Announces Open-Access Publishing Venture

The Bill & Melinda Gates Foundation is set to launch its own open-access publishing venture later this year. The initiative, Gates Open Research, will be modeled on a service begun last year by the London-based biomedical charity, the Wellcome Trust. Like that effort, the Gates Foundation’s platform is intended to accelerate the publication of articles and data from research funded by the charity. [Nature News] Editorial

Canada Budget Falls Flat with Scientists

The budget that Canadian Prime Minister Justin Trudeau’s government released lives up to his promises to emphasize innovation, and to encourage links between industry and academia. But it also presents scientists with a depressing, and unexpected, freeze on the main funding streams for basic research. [Nature News] Editorial

South Korea’s Scientists Seek Change amid Political Chaos

When South Korea’s Constitutional Court removed scandal-ridden President Park Geun-hye from office on 10^th March, citizens rejoiced in the streets — and many scientists breathed a sigh of relief. Her downfall has inspired a public appetite for broad governmental reforms, including changes in how the country supports scientific research. Many in the research community hope to end South Korea’s decades-long focus on applied research and shift more resources to basic science. [Nature News] Editorial

NEW European Immunogenetics and Histocompatibility Conference (EFI)
May 30-June 2, 2017
Heidelberg, Germany

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NEW Postdoctoral Fellow – Biomedicine (University of Bergen)

NEW Postdoctoral Positions – Computational Biology (The University of Texas MD Anderson Cancer Center)

Research Technologist – Cell Separation & Immunology (STEMCELL Technologies, Inc.)

Postdoctoral Research Fellowship – Tumor Immunology (University of Oslo)

Postdoctoral Position – Translational Immunology (German Cancer Research Center)

PhD Student Position – Mucosal Immunology (Karolinska Institutet)

Principal Scientist – Immuno Oncology (Celgene Corporation)

Postdoctoral Researcher – Development of Immune System (Lund University)

Research Investigator – Immuno-Oncology (Bristol-Meyers Squibb)

Associate/Full Professor – Immunobioengineering (University of Toronto)

Scientist – Immunology (Moderna Therapeutics)

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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