Immune Regulation News Volume 11.30 | Aug 16 2019

TOP STORY

Placental Growth Factor Regulates the Generation of T_H17 Cells to Link Angiogenesis with Autoimmunity

Researchers found that placental growth factor (PlGF), a homolog of the vascular endothelial growth factor that enhances an angiogenic switch in disease, was selectively secreted by the T_H17 subset of helper T cells and promoted angiogenesis. [Nat Immunol] Abstract

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Cryptic Activation of an Irf8 Enhancer Governs cDC1 Fate Specification

Scientists showed that cryptic activation of the +41-kb Irf8 enhancer in dendritic cell progenitors was responsible for classical type 1 dendritic cell fate specification. [Nat Immunol] Abstract

Neutrophil Extracellular Traps Initiate Gallstone Formation

Investigators found consistent evidence for the presence of neutrophil extracellular traps in human and murine gallstones and describe an immune-mediated process requiring activation of the innate immune system for the formation and growth of gallstones. [Immunity] Full Article

Gut-Associated IgA⁺ Immune Cells Regulate Obesity-Related Insulin Resistance

The authors showed that high fat diet feeding altered intestinal IgA⁺ immune cells and that IgA was a critical immune regulator of glucose homeostasis. Obese mice had fewer IgA⁺ immune cells and less secretory IgA and IgA-promoting immune mediators. [Nat Commun] Full Article | Press Release

Toxoplasma gondii Effector TgIST Blocks Type I Interferon Signaling to Promote Infection

Researchers demonstrated that TgIST, a secreted effector previously implicated in blocking type II IFN-γ signaling, also blocked IFN-β responses by inhibiting STAT1/STAT2-mediated transcription in infected cells. [Proc Natl Acad Sci USA] Abstract

Enhanced Adaptive Immune Responses in Lung Adenocarcinoma through Natural Killer Cell Stimulation

After stimulation, natural killer (NK) cells localized inside tumors, with increased cytokine production capacity. T cells were also recruited to tumors in an NK cell-dependent manner, and exhibited higher functionality. In neoantigen-expressing tumors, NK cell stimulation enhanced the number and function of tumor-specific T cells and, in long-term settings, reduced tumor growth. [Proc Natl Acad Sci USA] Full Article

Pro-Survival Lipid Sphingosine-1-Phosphate Metabolically Programs T Cells to Limit Anti-Tumor Activity

The authors discovered a direct correlation between sphingosine kinase 1 (SphK1)-generated S1P and lipid transcription factor peroxisome proliferator-activated receptor gamma activity, which in turn regulated lipolysis in T cells. Genetic and pharmacologic inhibition of SphK1 improved metabolic fitness and anti-tumor activity of T cells against murine melanoma. [Cell Rep] Full Article | Graphical Abstract

Maternal Antibodies Inhibit Neonatal and Infant Responses to Vaccination by Shaping the Early-Life B Cell Repertoire within Germinal Centers

Using murine early-life immunization models mimicking the condition prevailing in humans, researchers observed the induction of CD4-T, T follicular helper, and germinal center B cell responses even when early-life antibody responses were abrogated by maternal antibodies. [Cell Rep] Full Article | Graphical Abstract

T Cell Acute Lymphoblastic Leukemia Displays Autocrine Production of Interleukin-7

Using T cell acute lymphoblastic leukemia (T-ALL) cell lines, primary and patient-derived xenotransplanted T-ALL cells, scientists demonstrated that T-ALL cells produced IL-7 whereas normal T cells did not. [Oncogene] Abstract

The NEDD8-Activating Enzyme Inhibitor MLN4924 Sensitizes a TNFR1⁺ Subgroup of Multiple Myeloma Cells for TNF-Induced Cell Death

Investigators found that a subgroup of multiple myeloma cell lines and about half of the primary myeloma samples tested were sensitized to TNF-induced cell death by MLN4924. [Cell Death Dis] Full Article

Kaempferol Attenuates Imiquimod-Induced Psoriatic Skin Inflammation in a Mouse Model

Kaempferol reduced CD3⁺ T cell infiltration and gene expression of major proinflammatory cytokines, including IL-6, IL-17A and TNFα, in the psoriatic skin lesion. [Clin Exp Immunol] Abstract

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Metabolic Coordination of T Cell Quiescence and Activation

Initial studies focused on the immune receptors and transcriptional regulators involved in T cell quiescence and activation, but recent findings highlight cell metabolism as a crucial regulator of these processes. The authors summarize these intrinsic metabolic programs and also describe how cell-extrinsic factors, such as nutrients and regulatory T cells, directly and indirectly balance quiescence and activation programs in conventional T cells. [Nat Rev Immunol] Abstract

Engineering Universal Cells That Evade Immune Detection

With the advent of pluripotent stem cells, CRISPR–Cas9 and other gene-editing technologies, the race to create ‘off-the-shelf’ donor cells that are invisible to the immune system (‘universal cells’) has started. One important approach for creating such cells involves the manipulation of genes required for immune recognition, in particular HLA class I and II proteins. [Nat Rev Immunol] Abstract

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AbbVie Receives FDA Approval of RINVOQ^™ (Upadacitinib), an Oral JAK Inhibitor for the Treatment of Moderate to Severe Rheumatoid Arthritis

AbbVie announced that the FDA has approved RINVOQ^™, a 15 mg, once-daily oral Janus kinase (JAK) inhibitor, for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. [AbbVie] Press Release

Immunic, Inc. Announces First Patient Enrolled in Investigator-Sponsored Proof-of-Concept Clinical Trial of IMU-838 for the Treatment of Patients with Primary Sclerosing Cholangitis

Immunic, Inc. announced enrollment of the first patient in an investigator-sponsored proof-of-concept clinical trial of IMU-838 for the treatment of patients with primary sclerosing cholangitis. [Immunic, Inc.] Press Release

Gritstone Oncology Announces First Patient Dosed with SLATE, its “Off-The-Shelf” Neoantigen Immunotherapy

Gritstone Oncology, Inc. announced that the first SLATE patient has been dosed. SLATE is an investigational immunotherapy directed at shared tumor-specific neoantigens which are derived from driver mutations, functionally important gene alterations recurrently observed in cancer patients. [Gritstone Oncology, Inc] Press Release

City of Hope Now Enrolling Patients for First-in-Human T Cell Trial for HPV-Associated Cancers

The first-in-human, Phase I T cell trial for patients who have human papillomavirus (HPV)-associated cancers that have relapsed, or are resistant to treatment, is now open at City of Hope. [City of Hope] Press Release

NKMax America Doses First Subject in Phase I Trial of SNK in Patients with Refractory Cancer

NKMax America announced that it has dosed the first subject in study SNK01-US01, a Phase I clinical trial evaluating SNK, an ex vivo expanded autologous natural killer cell therapeutic, in patients with pathologically confirmed cancer refractory to conventional therapy. [NKMax America (PR Newswire Association LLC.)] Press Release

Remestemcel-L to be Evaluated as Treatment for Chronic Graft Versus Host Disease in Planned Investigator-Initiated Trial

Mesoblast Limited announced that it intends to provide its allogeneic cell therapy product candidate remestemcel-L for evaluation under an investigator-initiated Investigational New Drug submission as a potential treatment in children with steroid-refractory chronic graft-versus-host disease. [Mesoblast Limited (GlobeNewswire, Inc.)] Press Release

Academia to FBI on Monitoring Chinese Scientists: “Tread Carefully”

Nearly two dozen higher education groups warn the government to be cautious when advising US research universities to keep an eye on students and faculty with ties to certain Chinese institutions. [The Scientist] Editorial

For a Decade, Francis Collins Has Shielded NIH—While Making Waves of His Own

Collins has helped shield National Institutes of Health (NIH) from threatened budget cuts as well as the upheaval that has shaken many other federal agencies under the Trump administration. [Nature News] Editorial

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NEW Laboratory Manager – Human Immunology (Karolinska Institutet)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Research Associate – Human Immunology (STEMCELL Technologies Inc.)

Scientist – Human Immunology (STEMCELL Technologies Inc.)

Research Associate – Immune Cell Culture (STEMCELL Technologies Inc.)

Postdoctoral Position – Cell Death, Inflammation and Immunity (University Hospital of Cologne)

Professorship – Innate Immunity and Cardiovascular Repair (Goethe University Frankfurt am Main)

Staff Scientist – Lead Immunotherapy Bioinformatician (Fred Hutchinson Cancer Research Center)

Assistant Professor – Neuro-Immune/Neuro-Pharmacological Interactions (University of Pennsylvania)

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

Postdoctoral Fellow – Quantitative Microscopy of Immune Cells (National Institute on Aging)

Associate or Full Professor – Neuro-Immune/Neuro-Pharmacological Interactions (University of Pennsylvania)

Postdoctoral Fellow – TCR Immunology/Immune Therapy (The University of Texas MD Anderson Cancer Center)

Senior Scientist – Immuno-Oncology of Hematologic Malignancies (University of Kansas School of Medicine)

Postdoctoral Position – Immunology of Enteric Infections (University of Utah)

Assistant, Associate, or Full Professor – Cancer Immunotherapy/Tumor Immunology (University of California, Irvine)

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