Immune Regulation News Volume 12.17 | May 15 2020

TOP STORY

Cellular Locomotion Using Environmental Topography

Researchers showed that leukocytes could not only migrate under low adhesion but could also transmit forces in the complete absence of transmembrane force coupling. When confined within 3D environments, they used the topographical features of the substrate to propel themselves. [Nature] Abstract | Editorial

(Ranked by impact factor of the journal)

Developmental Relationships of Four Exhausted CD8⁺ T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms

The authors defined a four-cell-stage developmental framework for exhausted CD8⁺ T cells (Tex) cells. Two TCF1⁺ progenitor subsets were identified, one tissue restricted and quiescent and one more blood accessible, that gradually lost TCF1 as it divided and converted to a third intermediate Tex subset. [Immunity] Abstract | Graphical Abstract

A Small Molecule G6PD Inhibitor Reveals Immune Dependence on Pentose Phosphate Pathway

Investigators showed that the most widely cited glucose-6-phosphate dehydrogenase (G6PD) antagonist, dehydroepiandosterone, did not robustly inhibit G6PD in cells. They then identified a small molecule that more effectively inhibited G6PD. [Nat Cell Biol] Abstract | Graphical Abstract

Chemotaxing Neutrophils Enter Alternate Branches at Capillary Bifurcations

Researchers showed that pairs of neutrophils arriving closely one after another at capillary bifurcations migrated to alternating branches in vivo and in vitro. [Nat Commun] Full Article

Hepatocyte Mitochondria-Derived Danger Signals Directly Activate Hepatic Stellate Cells and Drive Progression of Liver Fibrosis

The release of mitochondria-derived damage-associated molecular patterns(mito-DAMPs) was controlled by efferocytosis of dying hepatocytes by phagocytic resident liver macrophages and infiltrating Gr-1(⁺) myeloid cells. Circulating mito-DAMPs were markedly increased in human patients with non-alcoholic steatohepatitis and significant liver fibrosis. [Nat Commun] Full Article

In Vivo Generation of CAR T Cells Selectively in Human CD4⁺ Lymphocytes

Scientists demonstrated the in vivo generation of CD19-CAR T cells using the CD8-targeted lentiviral vector CD8-LV. They investigated the in vivo generation of CD4-positive CAR T cells using CD4-targeted LV. [Mol Ther] Abstract | Graphical Abstract

Histones, DNA, and Citrullination Promote Neutrophil Extracellular Trap Inflammation by Regulating the Localization and Activation of TLR4

Investigators showed that histones, DNA, citrullination, and fragmentation synergized to drive inflammation below the histone cytotoxicity threshold. At low concentrations, nucleosomes induced cytokines, but high concentrations killed cells before cytokines were produced. [Cell Rep] Full Article | Graphical Astract

Zeb1 Represses TCR Signaling, Promotes the Proliferation of T Cell Progenitors and Is Essential for NK1.1⁺ T Cell Development

Scientists report that Zeb1 expression was induced early during T cell development in CD4^–CD8^– double-negative stage 2. Zeb1 expression was further increased in the CD4⁺CD8⁺ double-positive stage before decreasing in more mature T cell subsets. [Cell Mol Immunol] Abstract

IRAK4 Inhibition: A Promising Strategy for Treating RA Joint Inflammation and Bone Erosion

The authors showed that IRAK4 inhibitor therapy attenuated rheumatoid arthritis (RA) disease activity by blocking TLR7-induced M1 MΦ or fibroblast activation, as well as monokine-modulated Th1/Th17 cell polarization. [Cell Mol Immunol] Abstract

T-Cell Clones of Uncertain Significance Are Highly Prevalent and Show Close Resemblance to T-Cell Large Granular Lymphocytic Leukemia. Implications for Laboratory Diagnostics

In routine laboratory practice, T-cell clones of uncertain significance were detected in 42 of 159 patients without T-cell malignancy, and in 3 of 24 healthy donors. Their phenotype closely resembled that of 26 cases of T-cell large granular lymphocytic leukemia studied similarly, except for a much smaller clone size, slightly brighter CD2 and CD7, and slightly dimmer CD3 expression. [Mod Pathol] Abstract

Development of an Improved Murine Model of Necrotizing Enterocolitis Shows the Importance of Neutrophils in NEC Pathogenesis

Investigators evaluated the effects of altered neutrophil concentrations in neonatal mice while simultaneously undergoing a ecrotizing enterocolitis (NEC) induction. A total of 44 neonatal mice were included in this study and 40 were subjected to an established NEC induction paradigm and four were assigned a sham group. [Sci Rep] Full Article

High Efficiency CHO Cell Display-Based Antibody Maturation

Researchers improved the efficiency of this maturation system by reengineering activation-induced cytidine deaminase (AID), and optimizing the nucleic acid sequence of the target antibody gene and AID gene as well as the protocol for AID gene transfection. [Sci Rep] Full Article

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The Interplay between MicroRNAs and the Components of the Tumor Microenvironment in B-Cell Malignancies

The authors focus on the interplay between miRNAs and tumor microenvironment components in the different B-cell malignancies and its impact on diagnosis, proliferation, and involvement in treatment resistance. [Int J Mol Sci] Abstract | Graphical Abstract

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

FDA Grants Priority Review of Sutimlimab, Potential First Approved Treatment of Hemolysis in Adult Patients with Cold Agglutinin Disease

The FDA has granted priority review of Sanofi’s Biologics License Application for sutimlimab for the treatment of hemolysis in adult patients with cold agglutinin disease (CAD). Sutimlimab, an investigational monoclonal antibody, targets the underlying cause of hemolysis in CAD by selectively inhibiting complement C1s. [Sanofi] Press Release

Publishers Launch Joint Effort to Tackle Altered Images in Research Papers

The world’s largest science publishers are teaming up to discuss how to automatically flag altered or duplicated images in research papers. A new working group – the first formal cross-industry initiative to discuss the issue – aims to set standards for software that screens papers for problematic images during peer review. [Nature News] Editorial

Amid the COVID-19 Pandemic, Some Scientists Bring the Bench Home

While some scientists have turned to writing manuscripts and grants and making inventories of their freezers to keep busy while away from the bench, others have brought experiments home, turning bathrooms, laundry rooms, and kitchens into makeshift labs-sometimes seeing an opportunity to explore new questions, other times trying out of desperation to prevent projects from moving backwards. [The Scientist] Editorial

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NEW 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)

Postdoctoral Researcher – Immune Checkpoint Therapy (Canadian Nuclear Laboratories)

Chair – Department of Microbiology and Immunology (Western University)

Postdoctoral Fellow – Acute Myeloid Leukemia (Icahn School of Medicine at Mount Sinai)

Senior Scientist – Immunotherapy and Transplant Rejection (Regensburg Center for Interventional Immunology)

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

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