Immune Regulation News Volume 12.08 | Mar 6 2020

TOP STORY

Chlorotoxin-Directed CAR T Cells for Specific and Effective Targeting of Glioblastoma

Researchers found that chlorotoxin (CLTX) peptide bound a great proportion of tumors and constituent tumor cells. Chimeric antigen receptor (CAR) T cells using CLTX as the targeting domain mediated potent anti-glioblastoma (GBM) activity and efficiently targeted tumors lacking expression of other GBM-associated antigens. [Sci Transl Med] Abstract | Editorial

(Ranked by impact factor of the journal)

The Functional Activity of E-Cadherin Controls Tumor Cell Metastasis at Multiple Steps

Investigators found that E-cadherin expression persisted in metastatic lung nodules and circulating tumor cells in two mouse models of mammary cancer: genetically modified MMTV-PyMT mice and orthotopically grafted 4T1 tumor cells. [Proc Natl Acad Sci USA] Abstract

Regulatory CD8 T Cells That Recognize Qa-1 Expressed by CD4 T-Helper Cells Inhibit Rejection of Heart Allografts

The authors report that activation of regulatory CD8 T cells that recognized the Qa-1 class Ib major histocompatibility complex, a mouse homolog of human leukocyte antigen-E, inhibited antibody-mediated immune rejection of heart allografts. [Proc Natl Acad Sci USA] Abstract

Non-Canonical Caspase-1 Signaling Drives RIP2-Dependent and TNF-α-Mediated Inflammation In Vivo

Scientists report two mouse models of enzymatically inactive caspase-1-C284A, demonstrating the relevance of this pathway in vivo. In contrast to Casp1^−/− mice, caspase-1-C284A mice showed pronounced hypothermia and increased levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and IL-6 when challenged with lipopolysaccharide. [Cell Rep] Full Article | Graphical Abstract

Class IIa Histone Deacetylases Drive Toll-Like Receptor-Inducible Glycolysis and Macrophage Inflammatory Responses via Pyruvate Kinase M2

A proteomic screen identified the glycolytic enzyme pyruvate kinase M isoform 2 as a partner of pro-inflammatory histone deacetylase (Hdac) 7 in murine macrophages. Myeloid-specific Hdac7 overexpression in transgenic mice amplified lipopolysaccharide-inducible lactate and promoted a glycolysis-associated inflammatory signature. [Cell Rep] Full Article | Graphical Abstract

TRIM34 Attenuates Colon Inflammation and Tumorigenesis by Sustaining Barrier Integrity

Researchers identified a novel function of TRIM34 in goblet cells (GCs) in controlling inner mucus layer generation. Upon DSS treatment, TRIM34 deficiency led to a reduction in Muc2 secretion by GCs and subsequent defects in the inner mucus layer. [Cell Mol Immunol] Abstract

Thymic Stromal Lymphopoietin Protects in a Model of Airway Damage and Inflammation via Regulation of Caspase-1 Activity and Apoptosis Inhibition

The authors found that signaling through thymic stromal lymphopoietin (TSLP) receptor on non-hematopoietic cells was sufficient for TSLP’s protective function. Consistent with this finding, they showed that TSLP reduced caspase-1 and caspase-3 activity levels in primary human bronchial epithelial cells treated with bleomycin via Bcl-xL up-regulation. [Mucosal Immunol] Full Article

Pharmacological LRH-1/Nr5a2 Inhibition Limits Pro-Inflammatory Cytokine Production in Macrophages and Associated Experimental Hepatitis

Scientists demonstrated that pharmacological inhibition, along with liver receptor homolog-1 (LRH-1) knockdown, significantly reduced the lipopolysaccharide-induced production of pro-inflammatory cytokines in the macrophage line RAW 264.7 cells, as well as in primary murine macrophages. [Cell Death Dis] Full Article

Resveratrol Alleviates Obesity-Induced Skeletal Muscle Inflammation via Decreasing M1 Macrophage Polarization and Increasing the Regulatory T Cell Population

Resveratrol treatment decreased macrophage infiltration into skeletal muscle of high fat diet-fed mice. Resveratrol also led to the polarization of macrophages to the M2 direction, as well as decreasing the expression of a number of M1 pro-inflammatory cytokines. [Sci Rep] Full Article

Immunogenicity of Rat-Neu⁺ Mouse Mammary Tumors Determines the T Cell-Dependent Therapeutic Efficacy of Anti-Neu Monoclonal Antibody Treatment

Researchers investigated if the immunogenicity of the transplantable rat-neu⁺ tumor cell line (TUBO) derived from a BALB/c-NeuT primary tumor was associated with the response to anti-neu monoclonal antibody therapy. They compared the TUBO tumor outgrowth and tumor infiltrating T cells in isogenic and non-isogenic recipient mice. [Sci Rep] Full Article

Regulation of Lipid-Induced Macrophage Polarization through Modulating PPAR-γ Activity Affects Hepatic Lipid Metabolism via TLR4/NF-κB Signaling Pathway

RAW264.7 macrophages were treated with different fatty acids and cell culture supernatants were collected to prepare conditioned media (CM). Different co-culture systems between primary hepatocytes and CM from macrophages were established. [J Gastroenterol Hepatol] Abstract

SIRT3-Mediated Inhibition of FOS through Histone H3 Deacetylation Prevents Cardiac Fibrosis and Inflammation

Sirtuin 3 (SIRT3) knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1. Consistent with this, SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-α. [Signal Transduct Target Ther] Full Article

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Moving towards a Systems-Based Classification of Innate Immune-Mediated Diseases

The field of autoinflammation is moving from a gene-centric view of innate immune-mediated disease towards a systems-based concept, which describes how various convergent pathways, including pyrin and the actin cytoskeleton, protein misfolding and cellular stress, NF-κB dysregulation and interferon activation, contribute to the autoinflammatory process. [Nat Rev Rheumatol] Abstract

Neuroimmune Connections in Aging and Neurodegenerative Diseases

Investigators focus on the impact of central nervous system-resident cells of the innate immune system for the development of neurodegenerative diseases, review immune pathway genes that have been identified, and discuss the vicious cycle between inflammation and neurodegeneration. [Trends Immunol] Abstract

Evolution and Function of Interleukin-4 Receptor Signaling in Adaptive Immunity and Neutrophils

The authors review when IL-4R signaling cytokines appeared during evolution relative to neutrophils and adaptive immunity. Neutrophil-like granular phagocytes were present in invertebrates throughout the bilaterian clade, but the researchers are unable to find data on IL-4, IL-13, or their receptors in invertebrates. [Genes Immun] Full Article

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

Spring Bank Announces Clinical Collaboration to Evaluate SB 11285 in Combination with PD-L1 Checkpoint Inhibitor in Patients with Advanced Solid Tumors

Spring Bank Pharmaceuticals, Inc. announced a new clinical collaboration with Roche to explore the co-administration of SB 11285, Spring Bank’s intravenously-administered stimulator of interferon gene (STING) agonist with Roche’s PD-L1 checkpoint inhibitor atezolizumab in patients with advanced solid tumors. [Spring Bank Pharmaceuticals, Inc.] Press Release

Mount Sinai and Harbor BioMed Collaborate to Advance Novel Biotherapies for the Treatment of Cancer and Coronavirus COVID-19

Mount Sinai Health System and Harbor BioMed have entered into a multi-year, multifaceted collaboration to develop novel, fully human antibodies for the treatment and prevention of various diseases including oncology and immunology. The collaboration will also utilize the H2L2 Harbour Mice^® platform to generate monoclonal antibodies against the coronavirus SARS CoV 2 – COVID-19. [Harbour BioMed] Press Release

Can-Fite Is Filing Drug Safety Update Report Showing Positive Safety Results from Phase II and Phase III Studies of Namodenoson and Piclidenoson

Can-Fite BioPharma Ltd. announced it is submitting its annual Drug Safety Update Reports for both Piclidenoson and Namodenoson to the governing health regulatory agencies where its drug candidates are currently treating patients. [Can-Fite BioPharma Ltd.] Press Release

Trump Administration Expands Reach of EPA Secret Science Proposal

The US Environmental Protection Agency (EPA) released a controversial proposal to limit the scientific research used in the federal rule-making process. The draft “Strengthening Transparency in Regulatory Science” is part of the agency’s persistent effort to rework the foundation on which public health and environmental rules are crafted. [ScienceInsider] Editorial

China Bans Cash Rewards for Publishing Papers

Chinese institutions have been told to stop paying researchers bonuses for publishing in journals, as part of a new national policy to cut perverse incentives that encourage scientists to publish lots of papers rather than focus on high-impact work. [Nature News] Editorial

NEW World Vaccine Congress
April 6-9, 2020
Washington, DC, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellow – Leukemia Biology and Dendritic Cells (Dana Farber Cancer Institute)

Research Associate – Human Immunology (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Position – Leukocyte Extravasation across Postcapillary Venules (University Hospital of Muenster)

Postdoctoral Fellow – Immunometabolism (Braunschweig Univesity of Technology)

Postdoctoral Investigators – Single Cell Genomics (GlaxoSmithKline plc.)

Program Manager – Research Initiatives on Neurofibromatosis (Johns Hopkins University)

Postdoctoral Fellowships – Immunology (University of Oslo)

Postdoctoral Researcher – Immunoregulation (GlaxoSmithKline plc.)

Postdoctoral Scientist – Granuloma (Texas Biomedical Research Institute)

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

Biologist – Aging (NIH National Institute on Aging)

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