Human Immunology News Volume 8.04 | Feb 4 2020

TOP STORY

Nitric Oxide Orchestrates Metabolic Rewiring in M1 Macrophages by Targeting Aconitase 2 and Pyruvate Dehydrogenase

Researchers found that inflammatory macrophages re-routed pyruvate away from pyruvate dehydrogenase in an nitric oxide (NO)-dependent and hypoxia-inducible factor 1α-independent manner, thereby promoting glutamine-based anaplerosis. Ultimately, NO accumulation led to suppression and loss of mitochondrial electron transport chain complexes. [Nat Commun] Full Article

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lncRNA-AC006129.1 Reactivates a SOCS3-Mediated Anti-Inflammatory Response through DNA Methylation-Mediated CIC Downregulation in Schizophrenia

Researchers performed RNA sequencing of peripheral blood RNA from monozygotic twins discordant for schizophrenia, and identified a schizophrenia-associated upregulated long noncoding RNA (lncRNA) that participated in the inflammatory response by enhancing SOCS3 and CASP1 expression in schizophrenia patients and further validated this finding in AC006129.1-overexpressing mice showing schizophrenia-related abnormal behaviors. [Mol Psychiatry] Abstract

Glioblastomas Exploit Truncated O-Linked Glycans for Local and Distant Immune Modulation via the Macrophage Galactose-Type Lectin

Investigators demonstrated aberrant expression of glycans in different cancer types. These tumor-associated glycans triggered inhibitory signaling in tumor-associated macrophages and microglia through glycan-binding receptors. They investigated the glioblastoma glycocalyx as a tumor-intrinsic immune suppressor. [Proc Natl Acad Sci USA] Abstract

B7-H7 (HHLA2) Inhibits T-Cell Activation and Proliferation in the Presence of TCR and CD28 Signaling

The authors examined global transcriptomic changes in human T cells induced by B7-H7. Stimulation through TCR with OKT3 and B7-H7 resulted in modest fold changes in the expression of select genes; however, these fold changes were significantly lower than those induced by OKT3 and B7-1 stimulation. [Cell Mol Immunol] Full Article

Peripheral Innate Immune and Bacterial Signals Relate to Clinical Heterogeneity in Parkinson’s Disease

Monocyte subsets and expression of key surface markers were measured using flow cytometry. Serum markers including alpha-synuclein, inflammasome-related caspase-1 and bacterial translocation-related endotoxin were measured using quantitative immuno-based assays. [Brain Behav Immun] Abstract

Beta-Glycerophosphate-Induced ORAI1 Expression and Store Operated Ca²⁺ Entry in Megakaryocytes

Human megakaryocytic Meg01cells were exposed to 2mM of phosphate-donor ß-glycerophosphate for 24 hours. Platelets were isolated from blood samples of patients with impaired kidney function or control volunteers. [Sci Rep] Full Article

Imbalance in B Cell and T Follicular Helper Cell Subsets in Pulmonary Sarcoidosis

The authors found the altered distribution of peripheral B cell subsets with a predominance of “naïve” and activated B cell subsets and a decreased frequency of memory cell in peripheral blood of sarcoidosis patients was demonstrated. They found that in sarcoidosis patients there were increased levels of B cell subsets, which were previously shown to display regulatory capacities. [Sci Rep] Full Article

A Prevalent CXCR3⁺ Phenotype of Circulating Follicular Helper T Cells Indicates Humoral Dysregulation in Children with Down Syndrome

Scientists determinde the follicular helper (Tfh) and follicular regulatory T cell profile in the blood of children with Down syndrome (DS). Blood was collected from 24 children with DS, nine of whom had autoimmune diseases. Children with DS showed skewed Tfh differentiation towards the CXCR3⁺ phenotype: Tfh1 and Tfh1/17 subsets were increased, while Tfh2 and Tfh17 subsets were reduced. [J Clin Immunol] Abstract

Reduced-Intensity Haploidentical Peripheral Blood Stem Cell Transplantation Using Low-Dose Thymoglobulin for Aggressive Adult T Cell Leukemia/Lymphoma Patients in Non-Complete Remission

Complete remission was achieved in all the patients after transplantation. HTLV-I viral loads became undetectable after transplantation. No severe adverse events such as grade III-IV GVHD or viral/fungal diseases were observed. [Ann Hematol] Abstract

Artemisinin Sensitizes Tumor Cells to NK Cell-Mediated Cytolysis

Investigators report that Artemisinin sensitized tumor cells to NK cell cytolysis. Both human K562 and Raji tumor cells, and mouse YAC-1 tumor cells were more susceptible to human or mouse NK cell cytolysis in vitro after Artemisinin pretreatment. [Biochem Biophys Res Commun] Abstract

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Distribution and Storage of Inflammatory Memory in Barrier Tissues

The authors explore the impact of previous immune activity on various cell lineages with the goal of presenting a unified view of inflammatory memory to environmental exposures at barrier tissues. They propose that inflammatory memory is distributed across diverse cell types and stored through shifts in cell states, and they provide a framework to guide future experiments. [Nat Rev Immunol] Abstract

Clinical Application of Immune Checkpoints in Targeted Immunotherapy of Prostate Cancer

Immunosuppression in tumor microenvironment induced by non-functional T cells, tolerogenic dendritic cells, and regulatory T cells, has been reported to be the main obstacle to the effectiveness of anti-tumor immune responses induced by an immunotherapy method. [Cell Mol Life Sci] Abstract

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Alkahest Initiates a Phase II Clinical Trial of AKST4290 in Parkinson’s Disease with Funding from the Michael J. Fox Foundation

Alkahest, Inc. announced the dosing of the first patient in a Phase II clinical trial of AKST4290, an orally administered CCR3 inhibitor, for treatment of Parkinson’s disease. The trial, AKST4290-211, is funded in part by The Michael J. Fox Foundation for Parkinson’s Research and will evaluate the effect of AKST4290 on motor function and activities of daily living in patients with Parkinson’s disease. [Alkahest, Inc (GlobeNewswire, Inc.)] Press Release

Insmed Announces Positive Top-Line Results from Phase II WILLOW Study of INS1007 in Patients with Non-Cystic Fibrosis Bronchiectasis

Insmed Incorporated announced positive top-line results from its global, randomized, double-blind placebo-controlled Phase II WILLOW study evaluating the efficacy, safety, and pharmacokinetics of INS1007 administered once daily in adults with non-cystic fibrosis bronchiectasis. [Insmed, Inc.] 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

Why Did a Chinese University Hire Charles Lieber to Do Battery Research?

Among the ongoing mysteries surrounding last week’s arrest of Harvard University nanoscientist Charles Lieber is the precise nature of the research program Lieber was conducting in his cooperation with Chinese researchers. [ScienceInsider] Editorial

Cash from Cannabis Companies Creates Conflicted Researchers

Imagine that scientists charged with doing research on tobacco’s health implications were funded by tobacco companies. In fact, the tobacco industry used this tactic for decades to cast doubt on the adverse health effects of smoking. But today it would be an outrageous conflict of interest – research on addictive drugs shouldn’t be paid for by people who stand to profit from selling them. Yet this is exactly what is happening with cannabis. [STAT News] Editorial

NEW 2^nd Immuno-Metabolic Mechanisms of Atherosclerosis Conference
March 1-4, 2020
Nassau, Bahamas

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NEW Postdoctoral Fellow – T and B Cells in Celiac Disease (University of Oslo)

Scientist – Immunology (STEMCELL Technologies Inc.)

Research Associate – Human Immunology (STEMCELL Technologies Inc.)

Research Associate – Bioengineering (STEMCELL Technologies Inc.)

Professorship – Antimicrobial Resistance (University Hospital of Cologne)

Research Scientist – Immuno-Oncology (Ervaxx)

Chief – Division of Immunology (Boston Children’s Hospital)

Research Assistant Professor – Immunology (The University of Chicago)

Postdoctoral Fellowship – Breast Cancer Immunology and Immunotherapy (The University of Texas Southwestern Medical Center)

Postdoctoral Fellow – Immune Defense and HIV (Massachusetts General Hospital)

Postdoctoral Position – Blood Cancer Immunology (University Children’s Hospital Basel)

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