Immune Regulation News Volume 11.48 | Dec 20 2019

TOP STORY

A Class of γδ T Cell Receptors Recognize the Underside of the Antigen-Presenting Molecule MR1

Scientists describe a diverse population of human γδ T cells isolated from peripheral blood and tissues that exhibit autoreactivity to the monomorphic major histocompatibility complex-related protein 1 (MR1). [Science] Abstract | Press Release

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An Intrinsic Role of IL-33 in T_reg Cell-Mediated Tumor Immunoevasion

Researchers identified a cell-intrinsic role of the alarmin interleukin (IL)-33 in the functional stability of regulatory T (T_reg) cells. [Nat Immunol] Abstract

T Cells Instruct Myeloid Cells to Produce Inflammasome-Independent IL-1β and Cause Autoimmunity

Investigators describe an inflammasome-independent pathway of IL-1β production that was triggered upon cognate interactions between effector CD4⁺ T cells and mononuclear phagocytes. [Nat Immunol] Abstract

Immune Sensing of Cell Death through Recognition of Histone Sequences by C-Type Lectin-Receptor-2d Causes Inflammation and Tissue Injury

In a targeted screen of C-type lectin receptors, a Clec2d reporter responded to lysates from necrotic cells. Biochemical purification identified histones, both free and bound to nucleosomes or neutrophil extracellular traps, as Clec2d ligands. [Immunity] Abstract | Graphical Abstract

CD8⁺ T Cell-Mediated Endotheliopathy Is a Targetable Mechanism of Neuro-Inflammation in Susac Syndrome

The authors reveal the pathophysiology of Susac syndrome (SuS), an enigmatic neuroinflammatory disease with central nervous system (CNS) endotheliopathy. By investigating immune cells from the blood, cerebrospinal fluid, and CNS of SuS patients, they demonstrated oligoclonal expansion of terminally differentiated activated cytotoxic CD8⁺ T cells. [Nat Commun] Full Article

Chemical Functionality of Multidomain Peptide Hydrogels Governs Early Host Immune Response

Scientists evaluated the early inflammatory host response to four multidomain peptide hydrogels displaying amines, guanidinium ions, and carboxylates in a subcutaneous injection model. While all the studied peptide materials possessed similar nanostructure and physical properties, they triggered markedly different inflammatory responses. [Biomaterials] Abstract

Plasmacytoid Dendritic Cell Deficiency in Neonates Enhances Allergic Airway Inflammation via Reduced Production of IFN-α

Adoptive transfer of plasmacytoid dendritic cells (pDCs) or administration of IFN-α to neonatal mice prevented the development of allergic inflammation in wild type but not in IFNAR1^−/− mice. Similarly, adult mice developed more severe allergic inflammation when pDCs were depleted. [Cell Mol Immunol] Full Article

B7H4 Expression in Tumor Cells Impairs CD8 T Cell Responses and Tumor Immunity

Researchers assessed B7 homolog 4 (B7H4) expression cell types in human breast cancer tissues and addressed its potential mechanisms in the CD8 T cell immune response. [Cancer Immunol Immunother] Full Article

Toll-Like Receptor 4 Inhibition Prevents Autoimmune Diabetes in NOD Mice

The authors determined the role of TLR4 in the activation and proliferation of T lymphocytes in the onset of autoimmune diabetes, using the non-obese diabetic (NOD) mouse model. Antigen-specific activation and proliferation of diabetogenic T cells were assessed in vitro by carboxyfluorescein succinimidyl ester dilution, in presence of vehicle or CLI-095, a cyclohexene derivative that inhibited TLR4 signaling. [Sci Rep] Full Article

Contribution of ROS and Metabolic Status to Neonatal and Adult CD8⁺ T Cell Activation

Scientists evaluated the impact of the cytoplasmic and mitochondrial levels of reactive oxygen species (ROS) of adult and neonatal CD8⁺ T cells on their activation potential. They constructed a logical model connecting metabolism and ROS with T cell signaling. [PLoS One] Full Article

SP-D Attenuates LPS-Induced Formation of Human Neutrophil Extracellular Traps (NETs), Protecting Pulmonary Surfactant Inactivation by NETs

Investigators showed that an innate immune collectin, pulmonary surfactant protein-D (SP-D), attenuated lipopolysaccharide (LPS)-mediated NETosis in human neutrophils by binding to LPS. [Commun Biol] Full Article

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Exhaustion and Senescence: Two Crucial Dysfunctional States of T Cells in the Tumor Microenvironment

The authors discuss the unique phenotypic and functional characteristics of these two types of dysfunctional T cells and their roles in tumor development and progression. In addition, they further discuss the potential molecular and metabolic signaling pathways responsible for the control of T-cell exhaustion and senescence in the suppressive tumor microenvironment. [Cell Mol Immunol] Abstract

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Rheos Medicines Announces Worldwide Collaboration with Roche to Discover and Develop Novel Medicines in the Field of Immunometabolism

Rheos Medicines announced that it has entered into a worldwide exclusive collaboration, option and license agreement with Roche to discover, develop and commercialize novel therapeutics in the field of immunometabolism. [Rheos Medicines] Press Release

Turnstone Biologics Announces Global Collaboration and License Agreement with Takeda to Develop Novel Viral Immunotherapies

Turnstone Biologics announced a strategic collaboration with Takeda Pharmaceutical Company Limited to develop multiple products from its proprietary vaccinia virus platform targeting a broad range of cancer indications. [Turnstone Biologics (Business Wire, Inc.)] Press Release

New Phase III Study Shows Positive Results for Benlysta^® in Lupus Nephritis

The Lupus Research Alliance shared news from GSK that Benlysta demonstrated positive clinical trial results in treating lupus nephritis, a common complication of lupus causing inflammation of the kidneys that can result in end-stage kidney disease. [The Lupus Research Alliance] Press Release

Oncodesign Announces the Selection of Its First-in-Class RIPK2 Inhibitor Drug Candidate for Auto-Immune and Inflammatory Diseases

Oncodesign announced the selection of ODS-101 as a drug candidate for auto-immune and inflammatory disease indications. [Oncodesign] Press Release

Alligator Bioscience: First Patient Dosed with ATOR-1017 Developed for Metastasized Cancer

Alligator Bioscience announced that the first patient has been successfully dosed in the Phase I study with the wholly owned 4-1BB antibody ATOR-1017, which is being developed for the treatment of metastasized cancer. [Alligator Bioscience AB] Press Release

AbbVie Receives European Commission Approval of RINVOQ™ (Upadacitinib) for the Treatment of Adults with Moderate to Severe Active Rheumatoid Arthritis

AbbVie announced that the European Commission has approved RINVOQ™ for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs. [AbbVie, Inc.] Press Release

Agenus Commences Combination Trial of Its Next-Gen CTLA-4 with its PD-1 Antibody

Agenus Inc. announced the first patient dosed with AGEN1181, an anti-CTLA-4 antibody, in combination with balstilimab, Agenus’ PD-1 inhibitor. [Agenus, Inc.] Press Release

Grifols Launches XEMBIFY^® 20% Subcutaneous Immunoglobulin, a New Primary Immunodeficiency Treatment

Grifols announced the launch of its latest immunoglobulin innovation, XEMBIFY^®, the company’s first 20% subcutaneous immunoglobulin therapy for the treatment of patients two years of age and older with primary immunodeficiency. [Grifols] Press Release

2020 US Spending Bill Restricts Some Animal Research, Pushes for Lab Animal Retirement

Federal research agencies will be under increased pressure to reduce their use of monkeys, dogs, and cats when President Donald Trump signs the final 2020 US spending bill. [ScienceInsider] Editorial

Trump Picks Computer Scientist to Lead National Science Foundation

US President Donald Trump has nominated Sethuraman Panchanathan, a computer scientist researcher and vice-president at Arizona State University in Tempe, to be the next head of the National Science Foundation. [Nature News] Editorial

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