Immune Regulation News Volume 12.21 | Jun 12 2020

TOP STORY

Programmable Multistage Drug Delivery to Lymph Nodes

Researchers describe a delivery system to overcome lymphatic and intra-lymph node transport barriers by combining nanoparticles that were rapidly conveyed to draining lymph nodes after administration in peripheral tissues with programmable degradable linkers. [Nat Nanotechnol] Abstract

(Ranked by impact factor of the journal)

Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells

The authors demonstrated that tumor proteins were carried to the lymph node within discrete vesicles inside dendritic cells (DCs) and were then transferred among DC subsets. A synapse was formed between interacting DCs and vesicle transfer took place in the absence of free exosomes. [Cancer Cell] Abstract | Graphical Abstract

Distinct iNKT Cell Populations Use IFNγ or ER Stress-Induced IL-10 to Control Adipose Tissue Homeostasis

Using single-cell RNA sequencing, the authors found several adipose invariant natural killer T (iNKT) clusters, which they grouped into two functional populations based on NK1.1 expression. NK1.1^NEG cells almost exclusively produced IL-10 and other regulatory cytokines, while NK1.1^POS iNKT cells predominantly produced IFNγ. [Cell Metab] Abstract | Graphical Abstract

Metabolic Characteristics of CD8⁺ T Cell Subsets in Young and Aged Individuals Are Not Predictive of Functionality

Scientists investigated virtual memory T (T_VM) cell metabolism and its association with longevity and functionality. Elevated spare respiratory capacity is a feature of T_VM, but not antigen-experienced memory T, cells and it increased with age in both subsets. [Nat Commun] Full Article

Structural Basis for Oligoclonal T Cell Recognition of a Shared p53 Cancer Neoantigen

Investigators report structures of wild-type and mutant p53-HLA-A2 ligands, as well as structures of three tumor-specific T-cell receptors bound to p53R175H–HLA-A2. These structures revealed how a driver mutation in p53 rendered a self-peptide visible to T cells. [Nat Commun] Full Article

BACH2 Drives Quiescence and Maintenance of Resting Treg Cells to Promote Homeostasis and Cancer Immunosuppression

Researchers showed that BACH2 was re-purposed following T regulatory (Treg) lineage commitment and promoted the quiescence and long-term maintenance of resting Treg (rTreg) cells. Bach2 is highly expressed in rTreg cells but was down-regulated in activated Treg cells and during inflammation. [J Exp Med] Full Article

CD5 Dynamically Calibrates Basal NF-κB Signaling in T Cells during Thymic Development and Peripheral Activation

Scientists found that CD5 altered the basal activity of the NF-κB signaling in resting peripheral T cells. When CD5 was conditionally ablated, T cells were unable to maintain higher expression of the cytoplasmic NF-κB inhibitor IκBα. [Proc Natl Acad Sci USA] Abstract

Hepatocyte-Specific TAK1 Deficiency Drives RIPK1 Kinase-Dependent Inflammation to Promote Liver Fibrosis and Hepatocellular Carcinoma

Researchers discovered that inhibition of RIPK1 strongly suppressed inflammation induced by hepatocyte-specific loss of TAK1. Activation of RIPK1 promoted the transcription of key proinflammatory cytokines, such as CCL2, and CCR2⁺ macrophage infiltration. [Proc Natl Acad Sci USA] Abstract

Ligand-Induced Degradation of a CAR Permits Reversible Remote Control of CAR T Cell Activity In Vitro and In Vivo

Investigators created a CAR that was capable of on-demand downregulation by fusing the CAR to a previously developed ligand-induced degradation domain (LID). Addition of a small molecule ligand triggered exposure of a cryptic degron within the LID domain, resulting in proteasomal degradation of the CAR-LID fusion protein and loss of CAR on the surface of T cells. [Mol Ther] Abstract | Graphical Abstract

Chromatin Priming Renders T Cell Tolerance-Associated Genes Sensitive to Activation below the Signaling Threshold for Immune Response Genes

By performing an integrated analysis of signaling, epigenetic modifications, and gene expression, scientists demonstrated that immunological tolerance is established when both signaling to and chromatin priming of immune response genes were weakened. [Cell Rep] Full Article | Graphical Abstract

Long-Term Maintenance of Lung Resident Memory T Cells Is Mediated by Persistent Antigen

Using an adenovirus expressing influenza nucleoprotein (AdNP), investigators showed that CD8 tissue-resident memory cell (T_RM) in the lungs could be maintained for at least one year post vaccination. [Mucosal Immunol] Abstract

A Ligand-Independent Fast Function of RARα Promotes Exit from Metabolic Quiescence upon T Cell Activation and Controls T Cell Differentiation

The authors generated a mouse line where RARα is over-expressed in T cells to probe RARα function with unprecedented sensitivity. Using this model together with mice specifically lacking RARα in T cells, they found that RARα was required for prompt exit from metabolic quiescence in resting T cells upon T cell activation. [Mucosal Immunol] Abstract

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The Essential Functions of Mitochondrial Dynamics in Immune Cells

The authors discuss the role of mitochondrial dynamics in activation, differentiation, cytokine production, and the activity of related pathways in immune cells, particularly T cells, B cells, and other cells involved in the innate immune response. [Cell Mol Immunol] Abstract

Cytokines That Target Immune Killer Cells against Tumors

Investigators summarize the recent progress of these cytokines in both preclinical studies and selective clinical applications and discuss their perspectives on the development of new strategies to potentiate cytokine-based immunotherapy. [Cell Mol Immunol] Abstract

Inflammasome Activation and Regulation: Toward a Better Understanding of Complex Mechanisms

Scientists summarize the most recent advances and remaining challenges in understanding the ordered inflammasome assembly and activation upon sensing of diverse stimuli, as well as the tight regulations of these processes. [Cell Discov] Abstract

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

Sobi and Selecta Announce Strategic Licensing Agreement for SEL-212, a Phase III-Ready Novel Treatment for Chronic Refractory Gout

Swedish Orphan Biovitrum AB (Sobi™) and Selecta Biosciences, Inc. announced that the companies have entered into a strategic licensing agreement for the product candidate SEL-212. SEL-212 is a combination of Selecta’s tolerogenic ImmTOR immune tolerance platform and a therapeutic uricase enzyme that is designed to durably control serum uric acid and reduce immunogenicity. [Swedish Orphan Biovitrum AB] Press Release

Hong Kong’s Contentious National Security Law Concerns Some Academics

China’s plan to introduce a new security law in Hong Kong has prompted mixed reactions from scientists there. Some fear that such a law could lead to government interference in research, restrict participation in international collaborations and increase self-censorship, whereas others are confident that research will be unaffected. [Nature News] Editorial

NIH Strengthens Policies to Alert Agency to Sexual Harassment by Grantees

The National Institutes of Health (NIH) is tightening grant rules that until now have sometimes left the agency in the dark about sexual harassment cases involving researchers it supports. [ScienceInsider] Editorial

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NEW Research Associate – Cancer Immunology (King’s College London)

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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