Immune Regulation News Volume 10.34 | Sep 7 2018

TOP STORY

Notch Signaling Mediated by Delta-Like1/4 Ligands Controls the Pathogenesis of Chronic Graft-versus-Host Disease in Mice

Notch-deficient alloantigen-specific T cells showed no early defects in proliferation or helper polarization in vivo, but subsequently exhibited markedly decreased cytokine secretion and enhanced accumulation of FoxP3⁺ regulatory T cells. [Blood] Abstract

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SMAD4 Promotes TGF-β-Independent NK Cell Homeostasis and Maturation and Antitumor Immunity

Researchers demonstrated that selective deletion of Smad4 in natural killer (NK) cells led to dramatically reduced tumor cell rejection and augmented tumor cell metastases, reduced murine cytomegalovirus clearance, as well as impeded NK cell homeostasis and maturation. [J Clin Invest] Abstract | Full Article | Graphical Abstract

Microbiota-Derived Short-Chain Fatty Acids Promote Th1 Cell IL-10 Production to Maintain Intestinal Homeostasis

Investigators showed gut microbiota-derived short-chain fatty acids (SCFAs) promoted microbiota antigen-specific Th1 cell IL-10 production, mediated by G-protein coupled receptor 43. SCFAs activated Th1 cell STAT3 and mTOR, and consequently upregulated transcription factor B lymphocyte-induced maturation protein 1, which mediates SCFA-induction of IL-10. [Nat Commun] Full Article

Stage-Specific Epigenetic Regulation of CD4 Expression by Coordinated Enhancer Elements during T Cell Development

The authors showed that two stage-specific Cd4 cis-elements, the previously characterized enhancer E4p and a novel enhancer E4m, coordinately promoted Cd4 transcription in mature thymic MHC-II-specific T cells, in part through the canonical Wnt pathway. [Nat Commun] Full Article

Rapid CLIP Dissociation from MHC II Promotes an Unusual Antigen Presentation Pathway in Autoimmunity

Researchers generated knock-in non-obese diabetic mice with a single amino acid change in the chain–derived class II–associated invariant chain peptide (CLIP) segment of the invariant chain in order to moderately slow CLIP dissociation from I-A^g7. [J Exp Med] Abstract

The Human Lymph Node Microenvironment Unilaterally Regulates T-Cell Activation and Differentiation

Human tonsil and lymph node-derived fibroblastic reticular cells (FRCs) constrained the proliferation of both naïve and pre-activated T cells, skewing their differentiation away from a central memory T-cell phenotype. FRCs acted unilaterally without requiring T-cell feedback, imposing suppression via indoleamine-2,3-dioxygenase, adenosine 2A Receptor, prostaglandin E2, and transforming growth factor beta receptor. [PLoS Biol] Full Article | Press Release

Differential Requirement of Kindlin-3 for T Cell Progenitor Homing to the Non-Vascularized and Vascularized Thymus

In the thymus, kindlin-3 promoted intrathymic T cell proliferation by facilitating the integrin-dependent crosstalk with thymic antigen presenting cells, while intrathymic T cell migration, maturation into single positive CD4 and CD8 T cells and release into the circulation proceeded without kindlin-3. [Elife] Full Article

Control of Primary Mouse Cytomegalovirus Infection in Lung Nodular Inflammatory Foci by Cooperation of Interferon-Gamma Expressing CD4 and CD8 T Cells

Scientists found that the formation of nodular inflammatory foci (NIFs) was essential to reduce the number of infected cells in lung tissue, showing that NIFs were sites of infection as well as sites of immune response. T cells had to be present in NIFs in high numbers, and CD4 as well as CD8 T cells supported each other to efficiently control virus spread. [PLoS Pathog] Full Article

PP1α and Cofilin Regulate Nuclear Translocation of NFkB and Promote Expression of the Anti-inflammatory Cytokine IL-10 by T-cells

Researchers demonstrated that nuclear translocation of NF-kB was significantly inhibited in siRNA-mediated knock-down of protein phosphatase-1α (PP1α) or dominant-negative PP1α cells. Sub-population analysis revealed that defective nuclear translocation of NF-kB was most prominent in CD4⁺CD45RA^–CXCR3^– T-cells that included IL-10-producing T_H2 cells. [Mol Cell Biol] Abstract

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Forkhead Box Transcription Factors as Context-Dependent Regulators of Lymphocyte Homeostasis

Focusing on the various mechanisms by which their functional activity is modulated, as well as on their mechanisms of action, the authors discuss how specific forkhead box transcription factors control lymphocyte function, allowing for the establishment and maintenance of immune homeostasis. [Nat Rev Immunol] Abstract

Nutritional Modulation of Innate Immunity: The Fat–Bile–Gut Connection

Investigators summarize how nutrition modulates innate immunity. They discuss how the integration of postprandial signals by the gut microbiota, along with the absorption routes of metabolites, differentially affects immune niches to orchestrate immune responses. Finally, they discuss the potential consequences of these signals in the light of trained immunity. [Trends Endocrinol Metab] Abstract

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Checkmate Pharmaceuticals Announces Strategic Collaboration with Merck KGaA, Darmstadt, Germany and Pfizer to Evaluate Combination Therapy with CMP-001 and Avelumab

Checkmate Pharmaceuticals announced that it has entered into a clinical trial collaboration and supply agreement with the alliance between Merck KGaA, Darmstadt, Germany, and Pfizer to evaluate CMP-001, a TLR9 agonist, in combination with avelumab, a human anti-PD-L1 antibody. [Checkmate Pharmaceuticals] Press Release

Turnstone Biologics and the La Jolla Institute for Allergy and Immunology Enter into Strategic Collaboration for Personalized Neoantigen Immunotherapies

Turnstone Biologics and the La Jolla Institute for Allergy and Immunology announced that they have entered into a collaboration and licensing agreement whereby Turnstone will utilize La Jolla Institute’s proprietary neoantigen identification methodology to select personalized neoantigens to target with its proprietary viral technologies for the development of new cancer immunotherapies. [Turnstone Biologics (Business Wire, Inc.)] Press Release

Tezepelumab Granted Breakthrough Therapy Designation by US FDA

AstraZeneca and its partner Amgen Inc. announced that the US FDA has granted breakthrough therapy designation for tezepelumab in patients with severe asthma, without an eosinophilic phenotype, who are receiving inhaled corticosteroids/long-acting beta2-agonists with or without oral corticosteroids and additional asthma controllers. [AstraZeneca] Press Release

Update on TULIP 1 Phase III Trial for Anifrolumab in Systemic Lupus Erythematosus

AstraZeneca and MedImmune announced top-line results from the TULIP 1 Phase III trial for anifrolumab in adult patients with moderate-to-severe systemic lupus erythematosus (SLE). The trial did not meet the primary endpoint of a statistically-significant reduction in disease activity in patients with SLE as measured by the SLE Responder Index 4 at 12 months. [AstraZeneca] Press Release

Immusoft Receives $3.5 Million Grant to Expand upon Its Cell Therapy Platform

Immusoft Corporation announced that it has received a Phase II small business innovation research grant from the National Institute of General Medical Sciences, part of the National Institutes of Health. The grant, in the amount of just over $3.5 million, will enable Immusoft to further advance its modified B cell approach to treating disease. [Immusoft Corporation (Business Wire, Inc.)] Press Release

Peer Reviewers Unmasked: Largest Global Survey Reveals Trends

Scientists in developed countries provide nearly three times as many peer reviews per paper submitted as researchers in emerging nations, according to the largest ever survey of the practice. [Nature News] Editorial

FDA Official Says Trump’s New Limits on Hiring Foreign Scientists Makes It Harder to Attract Top Talent

The Trump administration’s restrictions on hiring foreign scientists are making it more difficult for the agency to attract top scientific talent, a top FDA official said. “[The policy] definitely has created an additional challenge, I think, for us,” said Melanie Keller, the FDA’s acting associate commissioner for scientific and clinical recruitment. [STAT News] Editorial

Russian Scientists Gain Access to Springer Nature Content through National License Agreement

Springer Nature and the Russian Foundation for Basic Research (RFBR) have signed a major agreement that will benefit researchers, post docs and students based at Russian research institutions. Oleg Belyavsky, Director of the Russian Foundation for Basic Research, said: “The launch of this national subscription is a highly important step for RFBR and the Russian research and academic community.” [Springer Nature Switzerland AG] Editorial

NEW Keystone Symposia: Uncovering Mechanisms of Immune-Based Therapy in Cancer and Autoimmunity
February 18-22, 2019
Breckenridge, Colorado, United States

NEW Keystone Symposia: Cancer Immunotherapy – Mechanistic Insights to Improve Clinical Benefit
March 10-14, 2019
Whistler, British Columbia, Canada

NEW Keystone Symposia: Cancer Metastasis – The Role of Metabolism, Immunity and the Microenvironment
March 15-19, 2019
Florence, Italy

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NEW Faculty Position – Immunology (Vanderbilt University Medical Center)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellowship – Immunology (University of Nantes)

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Postdoctoral Fellowships – Immunology and Single-Cell Transcriptomic Analysis (Luxembourg Institute of Health)

Postdoctoral Fellow/Research Scientist – Cancer Research (Icahn School of Medicine at Mount Sinai)

Department Chair – Inflammation & Immunity (Cleveland Clinic – Lerner Research Institute)

Research Associate – Innate Immune Response to Bacterial Infection (Imperial College London)

Faculty Position – Aging and the Immune System (Mayo Clinic)

Postdoctoral Researcher – Immunology, Inflammation and Aging (German Center for Neurodegenerative Diseases)

Postdoctoral Fellow – Immunotherapy (California Institute for Biomedical Research)

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