Immune Regulation News Volume 12.03 | Jan 31 2020

TOP STORY

Macrophage Metabolism of Apoptotic Cell-Derived Arginine Promotes Continual Efferocytosis and Resolution of Injury

Investigators found that continual efferocytosis was enhanced by the metabolism of apoptotic cell (AC)-derived arginine and ornithine to putrescine by macrophage arginase 1 and ornithine decarboxylase. Putrescine augments HuR-mediated stabilization of the mRNA encoding the GTP-exchange factor Dbl, which activated actin-regulating Rac1 to facilitate subsequent rounds of AC internalization. [Cell Metab] Abstract | Graphical Abstract

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Lymphatic Endothelial Cells Prime Naïve CD8⁺ T Cells into Memory Cells under Steady-State Conditions

Researchers showed that while many proliferating lymphatic endothelial cells-educated T cells entered early apoptosis, the remainders comprised a long-lived memory subset, with transcriptional, metabolic, and phenotypic features of central memory and stem cell-like memory T cells. In vivo, these memory cells preferentially homed to lymph nodes and display rapid proliferation and effector differentiation following memory recall, and could protect mice against a subsequent bacterial infection. [Nat Commun] Full Article

Vaccination with CD47 Deficient Tumor Cells Elicits an Antitumor Immune Response in Mice

Investigators showed that elimination of CD47, a ligand for the myeloid cell inhibitory receptor SIRPα, from tumor cells by genetic deletion or antibody blocking, significantly improved the effectiveness of the immune response to tumor cells. In both solid and hematopoietic mouse tumor models, vaccination with tumor cells or tumor antigen-expressing cells, that lack CD47 or were pre-coated with anti-CD47 antibodies, achieved an anti-tumor immune response. [Nat Commun] Full Article

Remethylation of Dnmt3a^−/− Hematopoietic Cells Is Associated with Partial Correction of Gene Dysregulation and Reduced Myeloid Skewing

To determine whether the hypomethylation phenotype of Dnmt3a^−/− hematopoietic cells is reversible, researchers developed an inducible transgene to restore expression of DNMT3A in transplanted bone marrow cells from Dnmt3a^−/− mice. Partial remethylation was detected within one week, but near-complete remethylation required six months. [Proc Natl Acad Sci USA] Full Article

Treg-Cell-Derived IL-35-Coated Extracellular Vesicles Promote Infectious Tolerance

Researchers induced CBA-specific, IL-35-producing Treg cells in Treg^Ebi3WT C57BL/6 reporter mice and identified IL-35 producers by expression of Ebi3^TdTom gene reporter plus Ebi3 and p35 proteins. Both subunits of IL-35 were displayed on the surface of tolerogen-specific Foxp3⁺ and Foxp3^neg T cells. [Cell Rep] Full Article | Graphical Abstract

MicroRNA miR-155 Is Required for Expansion of Regulatory T Cells to Mediate Robust Pregnancy Tolerance in Mice

The authors showed miR-155 is induced in the uterine mucosa and draining lymph nodes during the female immune response to male seminal fluid alloantigens. Mice with null mutation in miR-155 exhibited a reduced CD4⁺ T cell response after mating, with a disproportionate loss of CD25⁺FOXP3⁺ Treg cells. [Mucosal Immunol] Abstract

Protein Kinase 2 (CK2) Controls CD4⁺ T Cell Effector Function in the Pathogenesis of Colitis

Scientists determined that protein kinase 2 (CK2α) regulated CD4⁺ T cell proliferation through a cell-intrinsic manner. CK2α was also important in controlling CD4⁺ T cell responses by regulating NFAT2, which was vital for T cell activation and proliferation. [Mucosal Immunol] Abstract

Coordinated Signals from PARP-1 and PARP-2 Are Required to Establish a Proper T Cell Immune Response to Breast Tumors in Mice

Investigators bypassed the embryonic lethality of dually poly(ADP-ribose)-polymerase (PARP-1)/PARP-2-deficient mice by using a PARP-1-deficient mouse with a Cd4-promoter-driven deletion of PARP02 in T cells to investigate the understudied role of these PARPs in the modulation of T cell responses against AT-3-induced breast tumors. They found that dual PARP-1/PARP-2-deficiency in T cells promoted tumor growth while single deficiency of each protein limited tumor progression. [Oncogene] Abstract

Alterations in the Innate Immune System Due to Exhausting Exercise in Intensively Trained Rats

A short training program included two weeks of intensive training, ending with an exhaustion test. A second training program comprised five-week training including two exhaustion tests and three trainings per week. In this case, immune status was assessed before, immediately after and 24 hours after an additional final exhaustion test. [Sci Rep] Full Article

Hepatic ILC2 Activity Is Regulated by Liver Inflammation-Induced Cytokines and Effector CD4⁺ T Cells

Scientists showed that in homeostasis, hepatic innate lymphoid cells (ILC2) constituted a very small population with a naive, inactive phenotype. During immune-mediated hepatitis, the cytokines IL-33 and IFNγ were expressed in liver tissue. [Sci Rep] Full Article

Ketogenesis Activates Metabolically Protective γδ T Cells in Visceral Adipose Tissue

By using single-cell RNA sequencing of adipose-tissue-resident immune cells, the authors showed that the ketogenic diet (KD) expanded metabolically protective γδ T cells that restrained inflammation. Notably, long-term ad libitum KD feeding in mice causes obesity, impaired metabolic health and depleted the adipose-resident γδ T cells. [Nat Metab] Abstract

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Neutrophils as Regulators of Cardiovascular Inflammation

The authors discuss the influence of traditional and novel cardiovascular risk factors on neutrophil production and function. They then appraise the current knowledge of the contribution of neutrophils to the different stages of atherosclerosis, including atherogenesis, plaque destabilization and plaque erosion. [Nat Rev Cardiol] Abstract

Dynamic Post-Transcriptional Events Governing CD8⁺ T Cell Homeostasis and Effector Function

Investigators review gene-specific regulatory networks that define the magnitude and timing of cytokine production in CD8⁺ T cells. They discuss the dynamic features of post-transcriptional control during CD8⁺ T cell homeostasis and activation, and focus on the crosstalk between cell signaling and RNA-binding proteins. [Trends Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation research field.

Ervaxx and Cardiff University Enter Collaboration to Develop Novel T-Cell and T-Cell Receptor-Based Immunotherapeutics Targeting Dark Antigens™

Ervaxx™ has entered a licensing and research collaboration with a leading T-cell immunology group at Cardiff University. The new collaboration will support a multi-year research program with Prof. Andrew Sewell’s T-cell modulation group at Cardiff University focusing on the discovery and characterization of T-cells and T-cell receptor reactive to cancer-specific antigens and ligands, including Ervaxx’ proprietary Dark Antigens™. [Ervaxx™] Press Release

SQZ Biotech Announces First Patient Dosed in Phase I Trial of SQZ-PBMC-HPV for HPV⁺ Tumors

SQZ Biotechnologies (SQZ) announced that the first patient in its Phase I clinical trial of SQZ-PBMC-HPV has received their first dose. SQZ-PBMC-HPV is an autologous cell therapy candidate comprised of SQZ-engineered antigen presenting cells (APCs) designed to induce CD8 T cell responses against HPV16. [SQZ Biotechnologies] Press Release

Aphios Granted US Patent for Combination HIV Latency Nanotherapeutic towards an HIV Cure

Aphios Corporation announced that it was issued US Patent No. 10,493,030 for the treatment of HIV latency towards an HIV cure. [Aphios Corporation] Press Release

Feds Fund Innovative Health Research Happening at DAL, NSHA and IWK

Dalhousie University is home to four of the newest recipients of funding from the Government of Canada for their innovative health research. The $1,159,527 in funding is provided by the Canadian Institutes of Health Research Project Grants, which help researchers gather the kind of information they need to make real improvements to clinical practice, health service delivery, and public health policy. [Dalhousie University] Press Release

Scripps Acquires Pfizer’s Massive Microbial Library

The East Coast campus of the research institute received shipments of freeze-dried or frozen samples of more than 210,000 microbial strains, which scientists plan to mine for potentially useful natural products. [The Scientist] Editorial

Will Elizabeth Warren’s Stance against “Junk Science” Matter to Voters?

Senator Elizabeth Warren of Massachusetts has come out with a proposal to keep so-called junk science, supported by industry, out of federal policy decisions. Many scientists have pointed out that misleading research and evidence, raised to new prominence under the Trump administration, has led to environmental and health policies that endanger the public. The coming week may tell whether Warren’s approach resonates with people in a bellwether state. [Scientific American] Editorial

NEW EACR-AACR Basic and Translational Research Conference 2020 Conference: Tumor Microenvironment
March 2-4, 2020
Lisbon, Portugal

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NEW Postdoctoral Fellowships – Immunology (University of Oslo)

Research Associate – Human Immunology (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Immunoregulation (GlaxoSmithKline plc.)

Postdoctoral Scientist – Granuloma (Texas Biomedical Research Institute)

Postdoctoral Position – Computational Single-Cell Biology (Max Planck Institute of Immunobiology and Epigenetics)

Faculty Position – Ion Channels and Immunology (NYU School of Medicine)

Biologist – Aging (NIH National Institute on Aging)

Postdoctoral Fellowship – Immunology (Stanford University)

Tenure Track Position – Genetics/Genomics/Pharmacogenomics of Immune Function in Disease (University of Kentucky)

Postdoctoral Scholar Position – Molecular Biology, Immunology and Synthetic Biology (University of California, Irvine)

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