Immune Regulation News Volume 12.20 | Jun 5 2020

TOP STORY

Salt Generates Anti-Inflammatory Th17 Cells but Amplifies Their Pathogenicity in Pro-Inflammatory Cytokine Microenvironments

The authors demonstrated that high NaCl conditions induced a stable, pathogen-specific, anti-inflammatory Th17 cell fate in human T cells in vitro. The p38/MAPK pathway, involving NFAT5 and SGK1, regulated FoxP3 and interleukin-17A-expression in high-NaCl conditions. [J Clin Invest] Abstract | Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

IRAP-Dependent Endosomal T Cell Receptor Signaling Is Essential for T Cell Responses

Mechanistically, T cell receptor (TCR) ligation led to clathrin-mediated internalization of the TCR-CD3ζ complex, while maintaining CD3ζ signaling, in endosomal vesicles that contained the insulin responsive aminopeptidase (IRAP) and the SNARE protein Syntaxin 6. [Nat Commun] Full Article

MYC Functions as a Switch for Natural Killer Cell-Mediated Immune Surveillance of Lymphoid Malignancies

Investigators demonstrated a systemic reduction in NK cell numbers in SRα-tTA/Tet-O-MYC^ON mice bearing MYC-driven T-lymphomas. Residual mNK cells in spleens of MYC^ON T-lymphoma-bearing mice exhibited perturbations in the terminal NK effector differentiation pathway. [Nat Commun] Full Article

MHC-II Alleles Shape the CDR3 Repertoires of Conventional and Regulatory Naïve CD4⁺ T Cells

The authors established two mouse strains carrying distinct allelic variants of H2-A and analyzed thymic and peripheral production and T cell receptor repertoires of naïve conventional CD4⁺ T and naïve regulatory CD4⁺ T cells. [Proc Natl Acad Sci USA] Abstract

Nanoparticle Delivery of Immunostimulatory Oligonucleotides Enhances Response to Checkpoint Inhibitor Therapeutics

Scientists developed a modular nanoparticle system capable of encapsulating an array of immunostimulatory oligonucleotides that, in some cases, greatly increased their potency to activate inflammatory signaling within immune cells in vitro. [Proc Natl Acad Sci USA] Full Article

Neutrophil Swarming in Damaged Tissue Is Orchestrated by Connexins and Cooperative Calcium Alarm Signals

The authors showed that neutrophil swarms required mutual reinforcement of damage signaling at the wound core. New biosensors and live imaging in zebrafish revealed that neutrophil chemoattractant synthesis was triggered by a sustained calcium flux upon contact with necrotic tissue that required sensing of the damage signal ATP. [Curr Biol] Full Article | Graphical Abstract

Synthetic DNA-Delivery of an Engineered Arginase Enzyme Can Modulate Specific Immunity In Vivo

Strong immunosuppression of CD4 and CD8 T cell, as well as macrophages and dendritic cells was observed in vitro in presence of arginase-rich supernatant. To further evaluate the efficacy of DNA-encoded arginase on in vivo immunosuppression against an antigen, a cancer antigen vaccine model was used in presence or absence of DNA-encoded arginase. [Mol Ther Methods Clin Dev] Abstract | Full Article | Graphical Abstract

TonEBP in Dendritic Cells Mediates Pro-Inflammatory Maturation and Th1/Th17 Responses

Researchers report that the tonicity-responsive enhancer-binding protein, a Rel family protein involved in the pathogenesis of autoimmune disease and inflammation, was required for maturation and function of dendritic cells. [Cell Death Dis] Full Article

mTOR-Myc Axis Drives Acinar-to-Dendritic Cell Transition and the CD4⁺ T Cell Immune Response in Acute Pancreatitis

A mouse animal model of AP was established by repeated intraperitoneal injection of CAE. The mTOR inhibitor rapamycin was administered before acute pancreatitis induction. [Cell Death Dis] Full Article

Host Dysbiosis Negatively Impacts IL-9-Producing T-Cell Differentiation and Antitumor Immunity

Scientists analyzed the impact of the intestinal microbiota on the differentiation of colonic lamina propria IL-9-producing T cells in germ-free and dysbiotic mice. Systemic effects of the intestinal microbiota on IL-9-producing T cells and the anti-tumor role of IL-9 were analyzed in a model of melanoma-challenged dysbiotic mice. [Br J Cancer] Abstract

Resistance to Natural Killer Cell Immunosurveillance Confers a Selective Advantage to Polyclonal Metastasis

Investigators showed that polyclonal metastatic seeds exhibited higher resistance to NK cell killing. Using breast cancer models, they observed higher proportions of polyclonal lung metastasis in immunocompetent mice compared with mice lacking NK cells. [Nat Cancer] Abstract

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Creatine Metabolism: Energy Homeostasis, Immunity and Cancer Biology

The authors highlight the latest advances in creatine biology in tissues and cell types that have historically received little attention in the field. In adipose tissue, creatine controls thermogenic respiration and loss of this metabolite impairs whole-body energy expenditure, leading to obesity. [Nat Rev Endocrinol] Abstract

Regulation of Natural Killer Cell Activity by Glucocorticoids, Serotonin, Dopamine, and Epinephrine

Investigators review the effects of neuroendocrine factors on the different activities of NK cells. Understanding the effects of neuroendocrine factors on NK cell activities during physiological and pathophysiological conditions may result in novel therapeutic strategies to enhance NK cell functions against tumors. [Cell Mol Immunol] Abstract

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

Harbor BioMed Receives Chinese Regulatory Approval of IND Application to Begin Seamless Phase II/III Clinical Trial of HBM9161 in Graves’ Ophthalmopathy

Harbor BioMed announced that National Medical Products Administration approved its IND application for HBM9161, a full-human antibody targeting neonatal Fc receptor, to conduct a Phase II/II clinical trial in patients with Graves‘ ophthalmopathy. [Harbor BioMed] Press Release

NKMax America Receives FDA Clearance of IND for Phase I/IIa Trial of Their Natural Killer Cell Therapy (SNK01) in Combination with Trastuzumab or Cetuximab for the Treatment of Advanced/Metastatic HER2- or EGFR- Expressing Cancers

NKMax America announced that the FDA has cleared the company’s Investigational New Drug (IND) application for SNK01 in combination with trastuzumab or cetuximabfor the treatment of advanced/metastatic HER2- or EGFR- expressing cancers. [NKMax America] Press Release

As Pandemic Pounds US Universities, Federal Support Helps Their Labs Stay Afloat

This spring, as the coronavirus pandemic shuttered US higher education, many college presidents began to warn of the dire financial impact of a frozen US economy on their institutions. Their mix of revenue sources largely determined how much they might be hurt. [ScienceInsider] Editorial

NIH Grapples with Rush to Claim Billions in Pandemic Research Funds

For the second time in just over ten years, the National Institutes of Health (NIH) is scrambling to hand out billions of dollars in emergency research funding and scientists are rushing to get a piece of the action—even as some confusion and concerns abound. [ScienceInsider] Editorial

As the Pandemic Hits Campus Finances, Faculty Face Layoffs

The pandemic has bored holes in budgets at universities and colleges across the US and beyond. To stem the spread of the coronavirus, higher education institutions shuttered their campuses, sent students home, and moved classes online. [The Scientist] Editorial

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NEW Professor – Immunology (Lund University)

Postdoctoral Researcher – Genetic Engineering of Dendritic Cells (Aarhus University)

Postdoctoral Associate – G Protein-Coupled Receptors (Howard Hughes Medical Institute)

Postdoctoral Fellow – Mechanisms of Autoimmune Disease (Oklahoma Medical Research Foundation)

PhD Studentship – Antibody Diversity (University of Southern Denmark)

Postdoctoral Fellowships – Autoimmune Conditions (Benaroya Research Institute at Virginia Mason)

Postdoctoral Associate – Immunology and Mitochondrial Biology (Texas A&M Health Science Center)

Principle Scientist – Immunology and Gene Engineering (Empyrean Therapeutics Ltd)

Chair – Department of Microbiology and Immunology (Western University)

Principle Scientist – Cancer and Auto-Immune Disorders (Sanofi)

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