Immune Regulation News Volume 11.16 | May 10 2019

TOP STORY

Restriction of PD-1 Function by cis-PD-L1/CD80 Interactions Is Required for Optimal T Cell Responses

Researchers demonstrated that CD80 interacted with programmed cell death 1 ligand (PD-L1) in cis on antigen-presenting cells (APCs) to disrupt PD-L1/PD-1 binding. Subsequently, PD-L1 could not engage PD-1 to inhibit T cell activation when APCs expressed substantial amounts of CD80. [Science] Abstract

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Bhlhe40 Mediates Tissue-Specific Control of Macrophage Proliferation in Homeostasis and Type 2 Immunity

Scientists found that the transcription factor Bhlhe40 was required in a cell-intrinsic manner for the self-renewal and maintenance of large peritoneal macrophages, but not that of other tissue-resident macrophages. [Nat Immunol] Abstract

Fate-Mapping of GM-CSF Expression Identifies a Discrete Subset of Inflammation-Driving T Helper Cells Regulated by Cytokines IL-23 and IL-1β

To systematically study and manipulate granulocyte-macrophage colony-stimulating factor (GM-CSF)⁺ cells and their progeny in vivo, the authors generated a fate-map and reporter of GM-CSF expression mouse strain. They mapped the phenotypic and functional profile of auto-aggressive T helper (Th) cells during neuroinflammation and identified the signature and pathogenic memory of a discrete encephalitogenic Th subset. [Immunity] Abstract | Graphical Abstract

T-Bet Transcription Factor Promotes Antibody-Secreting Cell Differentiation by Limiting the Inflammatory Effects of IFN-γ on B Cells

Investigators showed that B cell intrinsic expression of interferon (IFN)-γR and the IFN-γ-induced transcription factor T-bet were required for T-helper 1 cell-induced differentiation of B cells into antibody-secreting cells. [Immunity] Abstract

Synthetic TRuC Receptors Engaging the Complete T Cell Receptor for Potent Anti-Tumor Response

Researchers report that T cell receptor fusion constructs comprising an antibody-based binding domain fused to T cell receptor (TCR) subunits can effectively reprogram an intact TCR complex to recognize tumor surface antigens. [Nat Commun] Full Article

Extracellular Vesicle Fibrinogen Induces Encephalitogenic CD8⁺ T Cells in a Mouse Model of Multiple Sclerosis

Scientists determined that plasma extracellular vesicles (pEVs) induced a spontaneous relapsing−remitting disease phenotype in MOG_35-55-immunized C57BL/6 mice. This modified disease phenotype was found to be driven by CD8⁺ T cells and required fibrinogen in pEVs. [Proc Natl Acad Sci USA] Abstract | Press Release

Regulation of Membrane Phospholipid Asymmetry by Notch-Mediated Flippase Expression Controls the Number of Intraepithelial TCRαβ⁺CD8αα⁺ T Cells

The authors demonstrated that the number of TCRαβ⁺CD8αα⁺ intestinal intraepithelial lymphocytes was severely reduced in mice lacking recombination signal binding protein for immunoglobulin kappa J region or Notch1 and Notch2 in T cells. [PLoS Biol] Full Article

Active Tonic mTORC1 Signals Shape Baseline Translation in Naive T Cells

Investigators reveal selective and robust tonic mTORC1 signals in CD4⁺ T cells that influence T cell fate decisions. They found that the Ras exchange factor Rasgrp1 was necessary to generate tonic mTORC1 signals. [Cell Rep] Full Article | Graphical Abstract

E3 Ubiquitin Ligase RNF170 Inhibits Innate Immune Responses by Targeting and Degrading TLR3 in Murine Cells

By immunoprecipitating toll-like receptor 3 (TLR3)-binding proteins in macrophages, researchers identified ring finger protein 170 (RNF170) as a TLR3-binding E3 ligase. RNF170 mediated the K48-linked polyubiquitination of K766 in the TIR domain of TLR3 and promoted the degradation of TLR3 through the proteasome pathway. [Cell Mol Immunol] Abstract

Increased β-Cell Proliferation before Immune Cell Invasion Prevents Progression of Type 1 Diabetes

Scientists report that enhancing β-cell mass early in life, in two models of female non-obese diabetic mice, resulted in immunomodulation of T cells, reduced islet infiltration and lower β-cell apoptosis, which together protected them from developing type 1 diabetes. [Nat Metab] Abstract

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Competition for Nutrients and Its Role in Controlling Immune Responses

The authors consider immune microenvironments where nutrients become limiting, the signaling alterations caused by insufficient nutrients, and the importance of nutrient availability in the regulation of immune responses. [Nat Commun] Full Article

The Presentation of Neuroendocrine Self‐Peptides in the Thymus: An Essential Event for Individual Life and Vertebrate Survival

Many studies, including the discovery of the transcription factors autoimmune regulator and fasciculation and elongation protein zeta family zinc finger, have shown that a defect in thymus central self‐tolerance is the earliest event promoting autoimmunity. [Ann N Y Acad Sci] Full Article

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Sensei Biotherapeutics Announces Clinical Trial Collaboration Agreement with AstraZeneca for Two Phase II Studies of SNS-301

Sensei Biotherapeutics, Inc. announced a clinical trial collaboration with AstraZeneca to evaluate the safety, tolerability and preliminary activity of AstraZeneca’s IMFINZI^®, a human monoclonal antibody directed against programmed death-ligand 1, in combination with SNS-301. [Sensei Biotherapeutics, Inc.] Press Release

Forty Seven Inc. and Acerta Enter Collaboration to Evaluate Novel Immuno-Oncology Triple Combination in Diffuse Large B-Cell Lymphoma

Forty Seven Inc. announced a collaboration with Acerta Pharma, AstraZeneca’s hematology research and development center of excellence. [Forty Seven Inc.] Press Release

Merus Announces First Patient Treated in Phase I Clinical Trial of MCLA-145 for Advanced Solid Tumors

Merus N.V. announced that the first patient has been treated in its Phase I trial evaluating safety, tolerability, and preliminary efficacy of MCLA-145 for the treatment of patients with advanced solid tumors. [Merus N.V.] Press Release

Xencor Doses First Patient in Phase I Study of XmAb^®23104 for the Treatment of Patients with Advanced Solid Tumors

Xencor, Inc. announced that the first patient has been dosed in XmAb23104-01, a Phase I clinical study to evaluate the safety and tolerability of XmAb23104, a bispecific antibody that simultaneously targets the immune receptors PD-1 and ICOS, for the treatment of patients with advanced solid tumors. [Xencor, Inc.] Press Release

BioLineRx Announces FDA Approval of IND Application for AGI-134, a Novel Immunotherapy Anti-Cancer Vaccine for Solid Tumors

BioLineRx Ltd. announced that the FDA has approved its Investigational New Drug (IND) application for AGI-134, a novel immunotherapy anti-cancer vaccine for solid tumors. [BioLineRx Ltd.] Press Release

Academics Raise Concerns About Predatory Journals on PubMed

The National Library of Medicine has quality control procedures in place, but some researchers believe additional scrutiny is necessary. [The Scientist] Editorial

Intolerance and Funding Concern Indian Scientists Ahead of Election

A rising intolerance towards intellectuals and minority groups in India has prompted scientists there to speak out ahead of the country’s mammoth general election. More than 200 scientists have signed an open letter appealing to citizens to reject the discrimination and violence being promoted by some extremist groups. [Nature News] Editorial

Brazilian Biomedical Science Faces Reproducibility Test

An ambitious project to test the reproducibility of biomedical experiments by Brazilian scientists is about to get under way. The Brazilian Reproducibility Initiative was launched last year by researchers at the Federal University of Rio de Janeiro. Now, the first wave of reproducibility testing is set to begin in August, with help from more than 60 laboratories scattered over 43 Brazilian research centers. [Nature News] Editorial

US Lawmakers Propose Plan to Reduce Primate Research at National Institutes of Health

The US National Institutes of Health (NIH) would be required to reduce its use of non-human primates in research, under a spending bill approved on 8 May by a committee in the US House of Representatives. The bill would direct the NIH “to accelerate efforts to reduce and replace the use of nonhuman primates with alternative research models” in its laboratories. [Nature News] Editorial

NEW Advanced Cell Therapies and Tissue Engineering
November 14-16, 2019
Milan, Italy

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NEW Postdoctoral Fellow – Innate Immunity and Inflammation (University of Pennsylvania)

NEW Postdoctoral Fellow – Intracellular Innate Immunity (EPFL)

Postdoctoral Fellow – Transplantation Immunology (Medical College of Wisconsin)

Professorship – Translational Immune Oncology (Uniklinik Köln)

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

Senior Staff Scientist – Functional Genomics (Wellcome Sanger Institute)

Director of Research – Division of Translational Medicine & Human Genetics (University of Pennsylvania)

Associate Scientist – Immuno-Oncology (HMH Center for Discovery & Innovation)

Postdoctoral Fellow – Cancer Checkpoint Immunotherapy (City of Hope)

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

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