Immune Regulation News Volume 11.31 | Aug 23 2019

TOP STORY

Mechanosensation of Cyclical Force by PIEZO1 Is Essential for Innate Immunity

Researchers showed that cyclical hydrostatic pressure, similar to that experienced by immune cells in the lung, initiated an inflammatory response via the mechanically activated ion channel PIEZO1. [Nature] Abstract

(Ranked by impact factor of the journal)

Dietary Intake Regulates the Circulating Inflammatory Monocyte Pool

Scientists showed that short-term fasting reduced monocyte metabolic and inflammatory activity and drastically reduced the number of circulating monocytes. [Cell] Full Article | Graphical Abstract

Effector T_H17 Cells Give Rise to Long-Lived T_RM Cells that Are Essential for an Immediate Response against Bacterial Infection

Using IL-17A tracking-fate mouse models, the authors found that a significant fraction of lung CD4 tissue resident memory T (T_RM) cells derived from IL-17A-producing effector (T_H17) cells following immunization with heat-killed Klebsiella pneumoniae. [Cell] Abstract | Graphical Abstract

Molecular Mechanisms of Lineage Decisions in Metabolite-Specific T Cells

In addition to the known mucosal-associated invariant T cell (MAIT)1 and MAIT17 effector subsets selected on bone-marrow-derived hematopoietic cells, investigators identified 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil-specific thymocytes that were selected on thymic epithelial cells and differentiated into CD44⁻ naive T cells. [Nat Immunol] Abstract

IL-1R3 Blockade Broadly Attenuates the Functions of Six Members of the IL-1 Family, Revealing Their Contribution to Models of Disease

Scientists developed a blocking monoclonal antibody to human IL-1R3 and demonstrated that this antibody specifically inhibited signaling via IL-1, IL-33 and IL-36 in vitro. [Nat Immunol] Abstract

Bhlhe40 and Bhlhe41 Transcription Factors Regulate Alveolar Macrophage Self‐Renewal and Identity

Investigators identified the transcription factors Bhlhe40 and Bhlhe41 as novel regulators of alveolar macrophages—a population that provides the first line of immune defense and executes homeostatic functions in lung alveoli. [EMBO J] Abstract | Graphical Abstract

Re-Education of Tumor-Associated Macrophages by CXCR2 Blockade Drives Senescence and Tumor Inhibition in Advanced Prostate Cancer

Researchers found that Pten-null prostate tumors were strongly infiltrated by tumor-associated macrophages expressing C-X-C chemokine receptor type 2 (CXCR2), and activation of this receptor through CXCL2 polarized macrophages toward an anti-inflammatory phenotype. [Cell Rep] Full Article | Graphical Abstract

T-Cell Expression of Bruton’s Tyrosine Kinase Promotes Autoreactive T-Cell Activation and Exacerbates Aplastic Anemia

The authors unexpectedly found high expression and activation of Bruton’s tyrosine kinase (BTK) in T cells. Deficiencies in BTK resulted in the impaired activation and proliferation of autoreactive T cells and ameliorated bone marrow failure in aplastic anemia. [Cell Mol Immunol] Full Article

MicroRNA-146a Negatively Regulates IL-33 in Activated Group 2 Innate Lymphoid Cells by Inhibiting IRAK1 and TRAF6

miR-146a directly inhibited type II innate lymphoid cell (ILC2) function and suppressed ILC2 proliferation both in vivo and in vitro. During stimulation of ILC2, miR-146a expression gradually increased with a decrease of cell proliferation. [Genes Immun] Abstract

Oncogenic Rag GTPase Signaling Enhances B Cell Activation and Drives Follicular Lymphoma Sensitive to Pharmacological Inhibition of mTOR

RRAGC mutations, targeted to the endogenous locus in mice, conferred a partial insensitivity to nutrient deprivation, but strongly exacerbated B cell responses and accelerated lymphomagenesis, while creating a selective vulnerability to pharmacological inhibition of mTORC1. [Nat Metab] Abstract

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Zebrafish in Inflammasome Research

Scientists discuss inflammasome research in zebrafish in light of current knowledge about mammalian inflammasomes. They summarize the evolutionary conservation of inflammasome components between zebrafish and mammals, highlighting the similarities and possible divergence in functions of these components. [Cells] Full Article

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NGen Funding to Transform Manufacturing of Critical Materials in Gene Therapies

NGen has approved Supercluster funding for a transformative $4.2 million project led by iVexSol Canada to develop an advanced manufacturing process for lentiviral vectors. [STEMCELL Technologies Inc.] Press Release

Exagen and the University of Washington Collaborate on Lupus and Rheumatoid Arthritis Research

Exagen Inc. announced a research collaboration with the University of Washington’s School of Medicine and Dr. Christian Lood, assistant professor of medicine, Division of Rheumatology. [Exagen Inc.] Press Release

Kalytera to Conclude Phase II Clinical Study and Initiate Phase III Study

Kalytera Therapeutics, Inc. announced that interim results from the company’s Phase II clinical study evaluating cannabidiol for the prevention of acute graft versus host disease are significantly positive, and, as a result, the company will not enroll the high dose cohort in its ongoing Phase II study, but will instead proceed directly to initiate a Phase III clinical registration study. [Kalytera Therapeutics, Inc.] Press Release

Knopp Biosciences Announces Start of Phase II Clinical Trial Evaluating Oral Dexpramipexole in Moderate-to-Severe Eosinophilic Asthma

Knopp Biosciences LLC announced the start of Phase II dose-ranging clinical trial in moderate-to-severe eosinophilic asthma. [Knopp Biosciences LLC] Press Release

Chi-Med Initiates a Phase I Trial of HMPL-523 in Patients with Immune Thrombocytopenia (ITP) in China

Hutchison China MediTech Limited has initiated a Phase I study of HMPL-523, its novel spleen tyrosine kinase inhibitor, in patients with ITP, an autoimmune disorder that can lead to increased risk of bleeding. [Hutchison China MediTech Limited] Press Release

Genmab Announces Approval of DARZALEX^® (Daratumumab) in Frontline Multiple Myeloma in Japan

Genmab A/S announced that the Ministry of Health, Labor and Welfare in Japan has approved the use of DARZALEX in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant. [Genmab A/S] Press Release

‘Paralysed by Anxiety’: Researchers Speak about Life in Troubled Ancient-DNA Lab

The University of Adelaide has suspended the leader and founder of its premier ancient-DNA centre, Alan Cooper, following an investigation into the ‘culture’ at the Australian centre. The university has not given a reason for its decision, but current and former co-workers of Cooper – an award-winning evolutionary biologist who specializes in human migration – have told Nature that he bullied them or that they watched him bully others. [Nature] Editorial

More Than 700 German Research Institutions Strike Open-Access Deal with Springer Nature

A consortium of more than 700 German research institutions and libraries announced an agreement with publisher Springer Nature to make it simpler for authors to publish their papers open access. The agreement is the largest national open-access deal to date, but it doesn’t allow authors to publish open access in Nature or its sister journals. [ScienceInsider] Editorial

As Brexit Nears, Britain’s Drugs, Devices and Pricing Regulators Seek the Exit

Firm details on exactly how the UK will regulate new medicines is still to be decided after it leaves the EU later this year (caveats on timing abound), but we now know that the regulator won’t be run by Dr. Ian Hudson, who is stepping down after six years in charge. [FierceBiotech] Editorial

NEW Cell Death in Immunity and Inflammation
October 6-9, 2019
Crete, Greece

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NEW Research Technologist (STEMCELL Technologies Inc.)

NEW Assistant Professor and Postdoctoral Fellows – Immunology (Chinese Academy of Sciences)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Research Associate – Human Immunology (STEMCELL Technologies Inc.)

Scientist – Human Immunology (STEMCELL Technologies Inc.)

Research Associate – Immune Cell Culture (STEMCELL Technologies Inc.)

Laboratory Manager – Human Immunology (Karolinska Institutet)

Postdoctoral Position – Cell Death, Inflammation and Immunity (University Hospital of Cologne)

Professorship – Innate Immunity and Cardiovascular Repair (Goethe University Frankfurt am Main)

Staff Scientist – Lead Immunotherapy Bioinformatician (Fred Hutchinson Cancer Research Center)

Assistant Professor – Neuro-Immune/Neuro-Pharmacological Interactions (University of Pennsylvania)

Postdoctoral Position – Computational Single-Cell Biology (Max Planck Institute of Immunobiology and Epigenetics)

Postdoctoral Fellow – Quantitative Microscopy of Immune Cells (National Institute on Aging)

Associate or Full Professor – Neuro-Immune/Neuro-Pharmacological Interactions (University of Pennsylvania)

Postdoctoral Fellow – TCR Immunology/Immune Therapy (The University of Texas MD Anderson Cancer Center)

Senior Scientist – Immuno-Oncology of Hematologic Malignancies (University of Kansas School of Medicine)

Postdoctoral Position – Immunology of Enteric Infections (University of Utah)

Assistant, Associate, or Full Professor – Cancer Immunotherapy/Tumor Immunology (University of California, Irvine)

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