Immune Regulation News Volume 12.05 | Feb 14 2020

TOP STORY

Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T-Cell Leukemogenesis

The authors identified a molecular mechanism responsible for reciprocal activation between Aurora B kinase (AURKB) and MYC. AURKB directly phosphorylated MYC at serine 67, counteracting GSK3β-directed threonine 58 phosphorylation and subsequent FBXW7-mediated proteasomal degradation. [Cancer Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Blockade of the Phagocytic Receptor MerTK on Tumor-Associated Macrophages Enhances P2X7R-Dependent STING Activation by Tumor-Derived cGAMP

Researchers generated an antibody that selectively inhibited efferocytosis by phagocytic receptor MerTK. Blockade of MerTK resulted in accumulation of apoptotic cells within tumors and triggered a type I interferon response. Treatment of tumor-bearing mice with anti-MerTK antibody stimulated T cell activation and synergized with anti-PD-1 or anti-PD-L1 therapy. [Immunity] Abstract | Graphical Abstract

Human Mast Cell Proteome Reveals Unique Lineage, Putative Functions, and Structural Basis for Cell Ablation

Scientists identified a mast-cell-specific proteome signature, indicative of a unique lineage, only distantly related to other immune cell types, including innate immune cells. Proteome comparison between human and mouse suggested evolutionary conservation of core mast cell functions. [Immunity] Abstract | Graphical Abstract

Cxcr4 Distinguishes HSC-Derived Monocytes from Microglia and Reveals Monocyte Immune Responses to Experimental Stroke

By combining Cxcr4-CreER-mediated lineage tracing with Cxcr4 inhibition or conditional Cxcr4 ablation in photothrombotic stroke, investigators found that Cxcr4 promoted initial monocyte infiltration and subsequent territorial restriction of monocyte-derived macrophages to infarct tissue. [Nat Neurosci] Abstract

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

The authors demonstrated that nitric oxide (NO) produced by murine macrophages was responsible for TCA cycle alterations and citrate accumulation associated with polarization. ¹³C tracing and mitochondrial respiration experiments mapped NO-mediated suppression of metabolism to mitochondrial aconitase. [Nat Commun] Full Article

Macrophages Employ Quorum Licensing to Regulate Collective Activation

Investigators showed that bimodal phenotypic partitioning of macrophages was primed during the resting state, dependent on cumulative history of cell density, predicted by extrinsic noise in transcription factor expression, and independent of canonical liposaccharide-induced intercellular feedback in the tumor necrosis factor response. [Nat Commun] Full Article

B Cells Migrate into Remote Brain Areas and Support Neurogenesis and Functional Recovery after Focal Stroke in Mice

To confirm a mechanistic role for B cells in functional recovery, rituximab was given to human CD20⁺ (hCD20⁺) transgenic mice to continuously deplete hCD20⁺-expressing B cells following transient middle cerebral artery occlusion. These mice experienced delayed motor recovery, impaired spatial memory, and increased anxiety through eight week poststroke compared to wild type littermates also receiving rituximab. [Proc Natl Acad Sci USA] Full Article

The Amount of BCL6 in B Cells Shortly after Antigen Engagement Determines Their Representation in Subsequent Germinal Centers

Scientists determined that B cell representation in stages before the germinal cancer (GC) compartment was related to BCL6 amounts. This was not by increased proliferation or suppression of early plasmablast differentiation, but rather by preferential recruitment and progression through these early stages of B cell activation, culminating in preferential transition into GC. [Cell Rep] Full Article | Graphical Abstract

Salt Sensing by Serum/Glucocorticoid-Regulated Kinase 1 Promotes Th17-Like Inflammatory Adaptation of Foxp3⁺ Regulatory T Cells

Investigators screened the Treg cell translatome and identified serum/glucocorticoid-regulated kinase 1 (SGK1), a known salt sensor in T cells, as being preferentially translated in activated Treg cells. Investigators showed that high salt drove thymic Treg cells to adopt a T helper type 17 (Th17)-like phenotype and enhanced generation of Th17-like induced Treg cells in a SGK1-dependent manner, all the while maintaining suppressive function. [Cell Rep] Full Article | Graphical Abstract

PDL1 Blockage Increases Fetal Resorption and Tfr Cells but Does Not Affect Tfh/Tfr Ratio and B-Cell Maturation During Allogeneic Pregnancy

Researchers introduced an allogeneic normal-pregnant mouse model and found that CD4⁺CXCR5^hiPD-1^hiFoxp3⁺T follicular regulatory (Tfr) cells were preferentially accumulated in the uterus at mid-gestation and displayed a distinct phenotype. In addition, the absence of PDL1 resulted in increased fetal resorption by favoring Tfr cell accumulation and upregulating PD-1 expression on these cells. [Cell Death Dis] Full Article

Microbial Regulation of Enteric Eosinophils and Its Impact on Tissue Remodeling and Th2 Immunity

The authors found that small intestinal eosinophilia was significantly greater in germ-free mice compared to specific pathogen free controls. This was associated with changes in the production of enteric signals that regulated eosinophil attraction and survival, and was fully reversed by complex colonization. [Front Immunol] Full Article

Restricted Immunological and Cellular Pathways Are Shared by Murine Models of Chronic Alcohol Consumption

Scientists investigated the common and specific pathways of Lieber-DeCarli diet (LD) and Meadows-Cook diet (MC) models. Livers from LD and MC mice were subjected to histologic changes, hepatic leukocyte population, hepatic transcripts level related to leukocyte recruitment, and hepatic RNA-seq analysis. Cross-species comparison was performed using the alcoholic liver disease transcriptomic public dataset. [Sci Rep] Full Article

Leukemia Inhibitory Factor Regulates the Activation of Inflammatory Signals in Macrophages and Trophoblast Cells

Researchers examined whether and how leukemia inhibitory factor (LIF) regulated the behavior of macrophages and trophoblast cells in response to pro-inflammatory stress factors. They found that LIF modulated the activating effects of interferon-gamma and granulocyte-macrophage colony-stimulating factor in macrophages and trophoblast cells by reducing the phosphorylation levels of signal transducer and activator of transcription-1 and -5. [Mol Immunol] Abstract | Graphical Abstract

Subscribe to our sister publications: Human Immunology News & Immunology of Infectious Disease News.

HCV Infection and Non-Hodgkin Lymphomas: An Evolving Story

The observation that hepatis C virus (HCV) eradication by antiviral treatment is associated with successful lymphoma response provided the most convincing evidence for the causal role of HCV in lymphoma’s development. According to the most accepted model, HCV-driven chronic antigenic stimulation may represent the major stimulus for lymphoma growth. [Clin Exp Med] Abstract

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

Can-Fite Completes 50% Patient Enrollment in Phase III Rheumatoid Arthritis Study and Implements Interim Analysis

Can-Fite BioPharma Ltd. announced it has completed enrollment of approximately 50% of the 525 patients planned for its Phase III ACRobat™ trial to evaluate its drug candidate Piclidenoson as a first-line treatment for rheumatoid arthritis. [Can-Fite BioPharma, Ltd.] Press Release

SELLAS Announces Enrollment of First Patient in Phase I Trial of Galinpepimut-S (GPS) in Combination with Nivolumab (Opdivo^®) in Patients with Malignant Pleural Mesothelioma (MPM)

SELLAS Life Sciences Group, Inc. announced the enrollment of the first patient in an investigator-sponsored clinical trial of its Wilms tumor-1-targeting peptide immunotherapeutic agent, GPS, in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, nivolumab, in patients with MPM. [SELLAS Life Sciences Group, Inc.] Press Release

Atreca Announces First Patient Dosed in Phase Ib Clinical Trial of ATRC-101 in Patients with Select Solid Tumors

Atreca, Inc. announced that the first patient has been dosed in a Phase Ib first-in-human clinical trial evaluating ATRC-101 in patients with select solid tumor cancers. ATRC-101, a monoclonal antibody derived from a human antibody identified in a cancer patient via Atreca’s drug discovery platform, targets a ribonucleoprotein complex and is believed to function through Driver Antigen Engagement, a novel mechanism of action in oncology. [Atreca, Inc.] Press Release

Harvard, Yale Investigated for Undisclosed Foreign Funding

The US Department of Education is investigating Harvard and Yale Universities for allegedly failing to disclose funds from other nations, according to a statement released February 12. First reported by the Wall Street Journal on Wednesday, the investigations are the latest in a series of efforts by the department to crack down on foreign influence in US institutions. [The Scientist] Editorial

Popular Preprint Servers Face Closure Because of Money Troubles

The rise of preprint repositories has helped scientists worldwide to share results and get feedback quickly. But several platforms that serve researchers in emerging economies are struggling to raise money to stay afloat. Repositories like INA-Rxiv and IndiaRxiv boost regional science, but finding cash to run them is proving difficult. [Nature News] Editorial

FDA Now Allows Certain Lab Animals to Be Retired and Adopted

The US Food and Drug Administration will now permit certain animals used in experiments to retire and be adopted rather than face euthanasia, according to internal documents reviewed by The Hill. Although the policy changed in November, there have not been any public statements from the agency. [The Scientist] Editorial

NEW Keystone Symposium: Advances in Cancer Immunotherapy
March 22-26, 2020
Whistler, British Columbia, Canada

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

NEW Postdoctoral Investigators – Single Cell Genomics (GlaxoSmithKline plc.)

NEW Postdoctoral Researcher – Brain Tumor Immunology (German Cancer Research Center)

Research Associate – Human Immunology (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

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)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Immune Regulation News? Click here to submit!

Comments or suggestions? Submit your feedback here.