Immune Regulation News Volume 10.44 | Nov 16 2018

TOP STORY

Small-Molecule Inhibitor of OGG1 Suppresses Proinflammatory Gene Expression and Inflammation

The authors developed TH5487, a selective active-site inhibitor of 8-oxoguanine DNA glycosylase 1 (OGG1), which hampered OGG1 binding to and repaired of 8-oxoG and which was well tolerated by mice. TH5487 prevented tumor necrosis factor-α-induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. [Science] Abstract | Press Release

(Ranked by impact factor of the journal)

RAS P21 Protein Activator 3 (RASA3) Specifically Promotes Pathogenic T Helper 17 Cell Generation by Repressing T Helper 2 Cell-Biased Programs

Researchers found that RASA3 was highly expressed by pathogenic Th17 (pTh17) cells relative to non-pTh17 cells and was required specifically for pTh17 generation in vitro and in vivo. Mice conditionally deficient for Rasa3 in T cells showed less pathology during experimental autoimmune encephalomyelitis. [Immunity] Abstract | Graphical Abstract

The Microbial Metabolite Butyrate Stimulates Bone Formation via T Regulatory Cell-Mediated Regulation of WNT10B Expression

Interaction of bone marrow CD8⁺ T cells with Treg cells resulted in increased secretion of Wnt10b, a bone anabolic Wnt ligand. Mechanistically, Treg cells promoted the assembly of a NFAT1-SMAD3 transcription complex in CD8⁺ cells, which drove expression of Wnt10b. [Immunity] Full Article | Editorial | Graphical Abstract

Commensal Bacteria Contribute to Insulin Resistance in Aging by Activating Innate B1a Cells

Using “healthy” aged mice and macaques, the authors found that insulin resistance was induced by activated innate 4-1BBL⁺ B1a cells. [Sci Transl Med] Abstract

Cellular Metabolism Constrains Innate Immune Responses in Early Human Ontogeny

Scientists showed transcriptomic, metabolic and polysome profiling and found that monocytes isolated from infants born early in gestation displayed perturbations in PPAR-γ-regulated metabolic pathways, limited glycolytic capacity and reduced ribosomal activity. [Nat Commun] Full Article

Permanent Neuroglial Remodeling of the Retina following Infiltration of CSF1R Inhibition-Resistant Peripheral Monocytes

Investigators showed that peripheral monocytes that infiltrate into the retina after ocular injury engraft permanently, migrate to the three distinct microglia strata, and adopt a microglia-like morphology. [Proc Natl Acad Sci USA] Full Article

Calnexin Impairs the Antitumor Immunity of CD4⁺ and CD8⁺ T Cells

Scientists found that calnexin, an endoplasmic reticulum chaperone protein, was significantly upregulated in oral squamous cell carcinoma (OSCC). Upregulation of its membranous expression on OSCC cells was associated with inhibited T-cell infiltration in tumor tissues and correlated with poor survival of OSCC patients. [Cancer Immunol Res] Abstract | Full Article

Mitochondrial p32/C1qbp Is a Critical Regulator of Dendritic Cell Metabolism and Maturation

Investigators demonstrated that p32/C1qbp, which functions as a multifunctional chaperone protein in mitochondria, supported mitochondrial metabolism and dendritic cell (DC) maturation. Metabolic analysis revealed that the citrate increase induced by lipopolysaccharide was impaired in p32-deficient DCs. [Cell Rep] Full Article | Graphical Abstract

Suppression of Murine Lupus by CD4⁺ and CD8⁺ T Regulatory Cells Induced by T-Cell Targeted Nanoparticles Loaded with IL-2 and TGF-β

Researchers developed a nanoparticle platform that could expand both CD4⁺ and CD8⁺ T regulatory cells in vivo for the suppression of autoimmune responses in systemic lupus erythematosus. [Arthritis Rheumatol] Abstract

Ezh2 Controls Skin Tolerance through Distinct Mechanisms in Different Subsets of Skin Dendritic Cells

The authors demonstrated that Ezh2 controls cutaneous tolerance by regulating Langerhans cell transmigration across the epidermal basement membrane directly via Talin1 methylation. [iScience] Abstract | Graphical Abstract | Full Article

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Effector and Regulatory B Cells in Immune-Mediated Kidney Disease

B cell-targeting biologics have been trialled with promising results in diverse immune-mediated renal conditions. These therapies can affect both pro-inflammatory B cells and regulatory B cells, potentially limiting their long-term efficacy. [Nat Rev Nephrol] Abstract

Non-Hematopoietic Control of Peripheral Tissue T Cell Responses: Implications for Solid Tumors

Scientists present the biochemical and biophysical mechanisms by which non-hematopoietic stromal cells and extracellular matrix molecules collaborate to regulate T cell behavior in peripheral tissue. They discuss how tissue remodeling in the context of tumor microenvironments impairs T cell accumulation and function contributing to immune escape and tumor progression. [Front Immunol] Full Article

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MorphoSys and I-Mab Sign Strategic Partnering Agreement for MorphoSys’s Novel Immuno-Oncology Agent MOR210

MorphoSys AG and I-Mab Biopharma jointly announced that they have entered into an exclusive strategic collaboration and regional licensing agreement for MOR210. [MorphoSys AG] Press Release

Fate Therapeutics Announces Encouraging Dose-Escalation Clinical Data of FATE-NK100 and Provides Regulatory Update on Landmark IND Application for FT500

Fate Therapeutics, Inc. announced new clinical data for FATE-NK100, an investigational, first-in-class, allogeneic donor-derived natural killer (NK) cell cancer immunotherapy, and provided a regulatory update on the development of FT500, a universal, off-the-shelf NK cell product candidate derived from a master induced pluripotent stem cell line. [Fate Therapeutics, Inc.] Press Release

Clinical Trial Harnesses Power of Natural Killer Cells to Treat Neuroblastoma

Researchers have made rapid advances in understanding how to manipulate the immune system safely to destroy cancer cells. Adoptive transfer of haploidentical natural killer (NK) cells has shown promise as a treatment option to target and kill cancer cells in a less toxic way than conventional therapies. Now for the first time, scientists will combine NK cell therapy with an immunocytokine to target children with relapsed/refractory neuroblastoma including those with bulky tumors. [Solving Kids’ Cancer] Press Release

STEM Candidates Elected to U.S. House Prepare for Their New Jobs

They’ve won their elections and are headed to Washington, D.C. Their next challenge is using their expertise to make Congress work better. [ScienceInsider] Editorial

Brexit: What the Draft Deal Means for Science

After two years of negotiations, the first real glimmers of what Brexit might involve have emerged. On 14 November, the Cabinet, the UK government’s senior decision-making body, backed a draft agreement on the terms of the country’s withdrawal from the European Union. For science, many of the details that will be most relevant are still to be thrashed out. [Nature News] Editorial

With Democrats in Control of U.S. House, Science Panel Gets Fresh Start

The results of divisive midterm elections, with Democrats reclaiming control of the U.S. House of Representatives and Republicans likely strengthening their hold on the Senate, have allowed both parties to claim victory. U.S. scientists are also experiencing mixed emotions. [ScienceInsider] Editorial

NEW Keystone Symposia: Neurodegenerative Diseases: New Insights and Therapeutic Opportunities
June 16-20, 2019
Keystone, Colorado, United States

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NEW Tenure-Track Assistant Professor – Cancer Immunology and Immunotherapy (University of Chicago)

NEW Faculty Positions – Translational Immunology (University of Miami)

NEW Postdoctoral Fellowship – Immune Oncology (Lund University)

Postdoctoral Position – Immunology and Ion Channel Function (New York University School of Medicine)

PhD Position – Cancer Immunotherapy (Helmholtz Zentrum München)

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)

Open Rank Professor – Biopharmaceutical Discovery (University of Delaware)

Assistant Professor – Biology (University of Delaware)

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

Postdoctoral Fellowship – Immunology (University of Nantes)

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

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