Immune Regulation News Volume 10.41 | Oct 26 2018

TOP STORY

Pathogen Blockade of TAK1 Triggers Caspase-8-Dependent Cleavage of Gasdermin D and Cell Death

The inhibition of TAK1 or IKK kinases by the Yersinia effector protein YopJ elicited RIPK1- and caspase-8-dependent cleavage of GSDMD, which subsequently resulted in cell death. [Science] Abstract

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T Cell-Intrinsic Receptor Interacting Protein 2 Regulates Pathogenic T Helper 17 Cell Differentiation

The authors showed that receptor interacting protein 2 deficiency in CD4⁺ T cells resulted in chronic and severe interleukin-17A-mediated inflammation during Chlamydia pneumoniae lung infection, increased T helper 17 cell formation in lungs of infected mice, accelerated atherosclerosis, and more severe experimental autoimmune encephalomyelitis. [Immunity] Abstract | Graphical Abstract

Cholesterol Homeostatic Regulator SCAP-SREBP2 Integrates NLRP3 Inflammasome Activation and Cholesterol Biosynthetic Signaling in Macrophages

Scientists have shown that NLRP3 inflammasome activation is integrated with the maturation of cholesterol master transcription factor SREBP2. Importantly, SCAP-SREBP2 complex endoplasmic reticulum-to-Golgi translocation was required for optimal activation of the NLRP3 inflammasome both in vitro and in vivo. [Immunity] Abstract | Graphical Abstract

LAG-3 Inhibits the Activation of CD4⁺ T Cells that Recognize Stable pMHCII through Its Conformation-Dependent Recognition of pMHCII

The authors identified a unique target selectivity for the inhibitory co-receptor LAG-3 that was intrinsic to its immunoregulatory roles. Although LAG-3 has been reported to recognize major histocompatibility complex (MHC) class II, it did not recognize MHC class II universally; instead, they found that it selectively recognized stable complexes of peptide and MHC class II (pMHCII). [Nat Immunol] Abstract

Antibiotics Induce Sustained Dysregulation of Intestinal T Cell Immunity by Perturbing Macrophage Homeostasis

Researchers showed that antibiotic use caused intestinal macrophages to become hyperresponsive to bacterial stimulation, producing excess inflammatory cytokines. Re-exposure of antibiotic-treated mice to conventional microbiota induced a long-term, macrophage-dependent increase in inflammatory T helper 1 responses in the colon and sustained dysbiosis. [Sci Transl Med] Abstract

IL-7 Receptor Blockade Blunts Antigen-Specific Memory T Cell Responses and Chronic Inflammation in Primates

Scientists investigated the therapeutic efficacy and mechanism of new anti-human IL-7Rα monoclonal antibodies (mAb) in non-human primates and show that, depending on the target epitope, a single injection of antagonistic anti-IL-7Rα mAbs induces a long-term control of skin inflammation despite repeated antigen challenges in presensitized monkeys. [Nat Commun] Full Article

Inhibition of Glucose Metabolism Selectively Targets Autoreactive Follicular Helper T Cells

Researchers showed that inhibiting glucose metabolism results in a drastic reduction of the frequency and number of follicular helper T (T_FH) cells in lupus-prone mice. However, this inhibition has little effect on the production of T-cell-dependent antibodies following immunization with an exogenous antigen or on the frequency of virus-specific T_FH cells induced by infection with influenza. [Nat Commun] Full Article

Phospholipid Flippases Enable Precursor B Cells to Flee Engulfment by Macrophages

Using the W3 T lymphoma cell line, investigators found that Ca²⁺ ionophore-induced phospholipid scrambling caused prolonged phosphatidylserine exposure in cells lacking both the ATP11A and ATP11C genes. ATP11C-null mutant mice exhibited severe B-cell deficiency. [Proc Natl Acad Sci USA] Abstract

Melatonin Suppresses TLR9-Triggered Proinflammatory Cytokine Production in Macrophages by Inhibiting ERK1/2 and AKT Activation

Investigators demonstrated that melatonin suppressed toll-like receptor 9 (TLR9) ligand-induced proinflammatory cytokines mRNA and protein production in peritoneal macrophages without interrupting the viability of peritoneal macrophages. [Sci Rep] Full Article

LncRNA HOTAIR Regulates Lipopolysaccharide-Induced Cytokine Expression and Inflammatory Response in Macrophages

Researchers investigated the potential role of a well-known lncRNA, HOTAIR, in inflammatory and immune response. They demonstrated that HOTAIR expression is induced in immune cells upon treatment with lipopolysaccharide. [Sci Rep] Full Article

Clodronate and Trabectedin Enhance Oncolytic Herpes Virotherapy in Preclinical Models of Ewing Sarcoma by Modulating the Tumor Immune Microenvironment

Scientists tested the effects of macrophage reduction using liposomal chlodronate and trabectedin on the antitumor efficacy of intratumoral oncolytic herpes simplex virus, rRp450, in two Ewing sarcoma xenograft models. Both agents enhanced antitumor efficacy without increasing virus replication. [Mol Ther Oncolytics] Abstract

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Anti-Inflammatory and Immune-Regulatory Cytokines in Rheumatoid Arthritis

Cytokine-mediated processes such as the activation of T helper 2 cells by IL-4 and IL-13, the resolution of inflammation by IL-9, IL-5-induced eosinophil expansion, IL-33-mediated macrophage polarization, the production of IL-10 by regulatory B cells and IL-27-mediated suppression of lymphoid follicle formation are all involved in governing the regulation and resolution of inflammation in rheumatoid arthritis. [Nat Rev Rheumatol] Abstract

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UCB and Biogen Announce Topline Results from a Phase IIb Study of Dapirolizumab Pegol in Systemic Lupus Erythematosus

UCB and Biogen Inc. announced top-line results from a Phase IIb study evaluating the safety and efficacy of dapirolizumab pegol, an anti-CD40L pegylated Fab, in adults with moderately-to-severely active systemic lupus erythematosus despite receiving standard-of-care treatment such as corticosteroids, anti-malarials and non-biological immunosuppressants. [Biogen Inc.] Press Release

CStone Receives US FDA IND Approval for Recombinant PD-1 mAb CS1003

CStone Pharmaceuticals announced that the FDA has recently granted approval to the company’s Investigational New Drug (IND) application for the independently developed recombinant humanized anti-programmed death-1 (PD-1) monoclonal antibody (mAb) CS1003. [CStone Pharmaceuticals (PR Newswire Association LLC.)] Press Release

Kadmon Initiates Pivotal Phase II Trial of KD025 in Chronic Graft-versus-Host Disease

Kadmon Holdings, Inc. announced that the first patient has been dosed in a pivotal clinical trial of KD025 in chronic graft-versus-host disease (cGVHD). The study will evaluate the efficacy and safety of KD025, Kadmon’s ROCK2 inhibitor, in adults with cGVHD who have received at least two prior lines of systemic therapy. [Kadmon Holdings, Inc.] Press Release

Font of Despair: In the Fierce Competition for Science Funding, Even a Typeface Glitch Can Be Fatal

To those experienced in requesting cash from both the Department of Veterans Affairs and the National Institutes of Health, rejection on the basis of margin or serif, if not the most pressing problem in biomedical research, is unsurprising and frustrating. [STAT News] Editorial

What a Massive Database of Retracted Papers Reveals about Science Publishing’s ‘Death Penalty’

Nearly a decade ago, headlines highlighted a disturbing trend in science: The number of articles retracted by journals had increased 10-fold during the previous 10 years. Fraud accounted for some 60% of those retractions; one offender, anesthesiologist Joachim Boldt, had racked up almost 90 retractions after investigators concluded he had fabricated data and committed other ethical violations. [ScienceInsider] Editorial

New Head of Indian Research Giant to Tackle Funding Issues and Red Tape

One of India’s largest and oldest research and development organizations has a new leader. Shekhar Mande, a structural biologist best known for his work on proteins, starts this month as director-general of the Council of Scientific and Industrial Research. [Nature News] Editorial

NEW Cell Symposia: Neuro-Immune Axis: Reciprocal Regulation in Development, Health, and Disease
September 22-24, 2019
Long Beach, California, United States

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NEW Research Technologist – Immunology (STEMCELL Technologies Inc.)

NEW Tenure/Tenure Track Faculty Position – Immunology (Wayne State University)

Postdoctoral Fellow – Immunology (Johns Hopkins University)

PhD Position – Antigen Presentation and Immune Regulation (Erasmus MC)

Postdoctoral Fellow – Immunology (Mondor Biomedical Research Institute)

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Faculty Position – Immunology (Benaroya Research Institute at Virginia Mason)

Institute Group Leader – Lymphocyte Biology (MD Anderson Cancer Center)

PhD and Postdoctoral Research Positions – Innate Immunity (Universitatsklinikum Tubingen)

Open Rank Professor – Biopharmaceutical Discovery (University of Delaware)

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Head of Laboratory – Immunology of Regulatory T Cells (Novartis Pharma AG)

Postdoctoral Fellow – Immuno-Oncology (Technical University of Munich)

Faculty Position – Immunology (Vanderbilt University Medical Center)

Postdoctoral Fellowship – Immunology (University of Nantes)

Postdoctoral Fellow – Foxp3+ T-Regulatory in Autoimmunity and Transplantation (Children’s Hospital of Philadelphia)

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