Immune Regulation News Volume 12.19 | May 29 2020

TOP STORY

Systemic Dysfunction and Plasticity of the Immune Macroenvironment in Cancer Models

Investigators used mass cytometry to define the systemic immune landscape in response to tumor development across five tissues in eight mouse tumor models. Systemic immunity was dramatically altered across models and time, with consistent findings in the peripheral blood of patients with breast cancer. [Nat Med] Abstract

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Single-Cell RNA Sequencing of Tumor-Infiltrating NK Cells Reveals that Inhibition of Transcription Factor HIF-1α Unleashes NK Cell Activity

Scientists defined the transcriptional landscape of mouse tumor-infiltrating NK cells by using single-cell RNA sequencing. Conditional deletion of Hif1a in NK cells resulted in reduced tumor growth, elevated expression of activation markers, effector molecules, and an enriched NF-κB pathway in tumor-infiltrating NK cells. [Immunity] Abstract | Graphical Abstract

Plasmacytoid Dendritic Cells and Type I Interferon Promote Extrafollicular B Cell Responses to Extracellular Self-DNA

The authors report that anti-DNA responses in Dnase1l3^-/- mice required CD40L-mediated T cell help, but proceed independently of germinal center formation via short-lived antibody-forming cells localized to extrafollicular regions. [Immunity] Abstract | Graphical Abstract

Selective AhR Knockout in Langerin-Expressing Cells Abates Langerhans Cells and Polarizes Th2/Tr1 in Epicutaneous Protein Sensitization

Researchers generated Langerin-specific and CD11c-specific knockout mice lacking aryl hydrocarbon receptor (AhR), respectively, in Langerhans cells and Langerin⁺ dermal dendritic cells and in all CD11c⁺ cells. These were then tested in an epicutaneous protein sensitization model. [Proc Natl Acad Sci USA] Abstract

Macrophages Use Distinct Actin Regulators to Switch Engulfment Strategies and Ensure Phagocytic Plasticity In Vivo

Investigators found that macrophage phagocytosis was highly robust, arising from their possession of two distinct modes of engulfment that utilize exclusive suites of actin-regulatory proteins. “Lamellipodial phagocytosis” was Arp2/3-complex-dependent and allowed cells to migrate toward and envelop apoptotic corpses. [Cell Rep] Full Article | Graphical Abstract

Therapeutic Efficacy of Anti-CD19 CAR-T Cells in a Mouse Model of Systemic Lupus Erythematosus

The authors constructed murine anti-CD19 CARs with either CD28 or 4-1BB as the intracellular costimulatory motif and evaluated the therapeutic function of the corresponding CAR-T cells by infusing them into MRL-lpr mice. [Cell Mol Immunol] Abstract

The RNA-Binding Protein Tristetraprolin Regulates RALDH2 Expression by Intestinal Dendritic Cells and Controls Local Treg Homeostasis

Scientists showed that Zfp36^−/− mice did not develop any histological signs of gut pathology. However, they displayed a clear increase in intestinal inflammatory markers and discrete alterations in microbiota composition. [Mucosal Immunol] Abstract

Pivotal Role of CD103 in the Development of Psoriasiform Dermatitis

Researchers report that CD103 regulates the development of psoriasiform dermatitis through the control of the function of conventional dendritic cells. Deficiency in CD103 exacerbated psoriasiform dermatitis, accompanied by excessive epidermal hyperplasia and infiltration of inflammatory leukocytes. [Sci Rep] Full Article

Skin Expression of IL-23 Drives the Development of Psoriasis and Psoriatic Arthritis in Mice

Investigators showed that mice expressing increased levels of IL-23 in the skin developed a psoriatic arthritis-like disease that was characterized by acanthosis, parakeratosis, hyperkeratosis, and inflammatory infiltrates in the dermis. [Sci Rep] Full Article

Dendritic Cells with METTL3 Gene Knockdown Exhibit Immature Properties and Prolong Allograft Survival

Bone marrow-derived dendritic cells from donor BALB/c mice were infected with lentiviruses expressing methyltransferase-like protein 3 (METTL3)-specific short hairpin RNA to silence METTL3. [Genes Immun] Abstract

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Recent Advances of Sterile Inflammation and Inter-Organ Cross-Talk in Alcoholic Liver Disease

Scientists summarize recent studies on the identification and understanding of damage-associated molecular patterns, their receptors, and cross-talk between the liver and other organs, and highlight successful therapeutic targets and potential strategies in drug development that can be used to combat alcoholic liver disease. [Exp Mol Med] Full Article

Immune Checkpoint Pathways in Immunotherapy for Head and Neck Squamous Cell Carcinoma

The authors summarize the functional mechanism and use of various immune checkpoint molecules in head and neck squamous cell carcinoma (HNSCC), including monotherapies and combination therapies, and provide better treatment options for patients with HNSCC. [Int J Oral Sci] Abstract

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FDA Approves Dupixent^® (Dupilumab) as First Biologic Medicine for Children Aged 6 to 11 Years with Moderate-to-Severe Atopic Dermatitis

FDA approved Dupixent^® for children aged six to 11 years with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. [Sanofi] Press Release

Aurinia Completes Submission of New Drug Application to the US Food & Drug Administration for Voclosporin for the Treatment of Lupus Nephritis

Aurinia Pharmaceuticals, Inc. announced the completion of the rolling submission of a New Drug Application to the FDA for voclosporin as a potential treatment for lupus nephritis, a serious inflammation of the kidneys caused by the autoimmune disease systemic lupus erythematosus. [Aurinia Pharmaceuticals, Inc.] Press Release

US Looks to Block Chinese Grad Students’ and Researchers’ Visas

Administration officials and lawmakers say the move is to shore up national security threats, but university professors argue such cancellations represent targeted discrimination. [The Scientist] Editorial

What the Growing Rift Between the US and WHO Means for COVID-19 and Global Health

Experts in health policy are contending with the real possibility that the United States will pull away from the World Health Organization (WHO), fracturing a relationship that began in the wake of the Second World War. [Nature News] Editorial

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NEW 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)

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

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

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