Immune Regulation News Volume 12.00 | Jan 10 2020

TOP STORY

Microbial Bile Acid Metabolites Modulate Gut RORγ⁺ Regulatory T Cell Homeostasis

Scientists report that both dietary and microbial factors influenced the composition of the gut bile acid pool and modulated an important population of colonic FOXP3⁺ regulatory T cells expressing the transcription factor RORγ. [Nature] Abstract | Press Release

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Adrenergic Signaling in Muscularis Macrophages Limits Infection-Induced Neuronal Loss

Using murine models of enteric infections, researchers observed long-term gastrointestinal symptoms, including reduced motility and loss of excitatory intrinsic enteric-associated neurons, which was mediated by a Nlrp6– and Casp11-dependent mechanism, depended on infection history, and could be reversed by manipulation of the microbiota. [Cell] Abstract | Graphical Abstract | Press Release

Regulatory T Cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis

The authors showed that regulatory T cells were a key source of TGFβ ligands and, accordingly, their depletion reprogrammed the fibroblast population, with loss of tumor-restraining, smooth muscle actin-expressing fibroblasts. [Cancer Discov] Abstract | Full Article

CDK7 Inhibition Potentiates Genome Instability Triggering Anti-Tumor Immunity in Small Cell Lung Cancer

Using a selective cyclin-dependent kinase 7 (CDK7) inhibitor, YKL-5-124, investigators demonstrated that CDK7 inhibition predominately disrupted cell-cycle progression and induced DNA replication stress and genome instability in small cell lung cancer while simultaneously triggering immune-response signaling. [Cancer Cell] Abstract | Graphical Abstract

Charting the cis-Regulome of Activated B Cells by Coupling Structural and Functional Genomics

Scientists assembled a functional cis-regulome for lipopolysaccharide-activated B cells. Functional enhancers, in contrast with accessible chromatin regions that lack enhancer activity, were enriched for enhancer RNAs and preferentially interacted in vivo with B cell lineage-determining transcription factors. [Nat Immunol] Abstract

Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4⁺ T Cells

Researchers examined the molecular and cellular mechanisms underpinning the differentiation of cytotoxic CD4⁺ T cells following immunotherapy. CD4⁺ transfer into lymphodepleted animals or regulatory T cell depletion promoted granzyme B expression by tumor-infiltrating CD4⁺, and this was prevented by interleukin-2 neutralization. [Immunity] Abstract | Graphical Abstract

PD-1 Imposes Qualitative Control of Cellular Transcriptomes in Response to T Cell Activation

The authors investigated how PD-1 affected transcriptome changes induced by T cell receptor (TCR) activation. They identified a huge variance in PD-1 sensitivity among TCR-inducible genes. [Mol Cell] Abstract | Graphical Abstract

Siah2 Control of T-Regulatory Cells Limits Anti-Tumor Immunity

Investigators report that growth of BRAF-mutant melanoma cells was inhibited, up to complete rejection, in Siah2^−/− mice. Growth-inhibited tumors exhibited increased numbers of intra-tumoral activated T cells and decreased expression of Ccl17, Ccl22, and Foxp3. [Nat Commun] Full Article | Press Release

Differential Expansion of T Central Memory Precursor and Effector Subsets Is Regulated by Division Speed

Scientists computationally reconstructed the proliferative history of single CD8⁺ T cells upon vaccination and measured the division speed of emerging T cell subsets in vivo. [Nat Commun] Full Article

Homeostasis and Transitional Activation of Regulatory T Cells Require c-Myc

Researchers report that the transcriptional regulator c-Myc (Myc) controlled immune homeostasis through regulation of T_reg accumulation and functional activation. Myc activity was enriched in T_regs generated during neonatal life and responding to inflammation. [Sci Adv] Full Article

RAMP1 Signaling in Immune Cells Regulates Inflammation-Associated Lymphangiogenesis

The number of CD11b⁺ cells from RAMP1^−/− mice was higher than wild-type mice and was associated with the upregulated expression of genes related to pro-inflammatory macrophage phenotype and downregulation of reparative macrophage phenotype-related expression. [Lab Invest] Abstract

Targeted Deletion of PD-1 in Myeloid Cells Induces Antitumor Immunity

The authors generated a conditional allele, which allowed myeloid-specific or T cell-specific targeting of Pdcd1 gene. Compared with T cell-specific PD-1 ablation, myeloid cell-specific PD-1 ablation more effectively decreased tumor growth. [Sci Immunol] Full Article

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The Metabolic Signature of T Cells in Rheumatoid Arthritis

T cells in patients with rheumatoid arthritis, even naïve T cells never having been involved in inflammatory lesions, have a unique metabolic signature and the changes in intracellular metabolites drive pathogenic T cell behavior. Recognizing the role of metabolic signals in cell fate decisions opens the possibility for immunomodulation long before the end stage synovial inflammation encountered in clinical practice. [Curr Opin Rheumatol] Abstract

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Arena Pharmaceuticals and Beacon Discovery Expand Strategic Relationship Focusing on Multiple Immune and Inflammatory Targets

Arena Pharmaceuticals, Inc. and Beacon Discovery announced that they entered into a strategic multi-year partnership aimed at building novel medicines across a range of G protein-coupled receptor targets. [Arena Pharmaceuticals, Inc.] Press Release

SAB Biotherapeutics Announces Research Collaboration with CSL Behring

SAB Biotherapeutics announced that it has entered into multiple collaboration and option agreements with CSL Behring. The collaborations will explore the possibility and the potential of new therapies to treat challenging autoimmune, infectious and idiopathic diseases by leveraging SAB’s DiversitAb™ platform. [SAB Biotherapeutics, Inc. (Business Wire, Inc.)] Press Release

Yisheng Biopharma and Tavotek Biotherapeutics Announce Strategic Research Alliance for Development of YS-ON-001/002 and Tavo-301/303 Combination Therapy for Cancer Treatment

Yisheng Biopharma Co., Ltd. and Tavotek Biotherapeutics announced that the companies have entered into a strategic research alliance and collaborate in the development involving their lead assets in oncology. [Yisheng Biopharma Co., Ltd. (PR Newswire Association, LLC.)] Press Release

Aclaris Therapeutics Announces Positive Results from Phase I Single and Multiple Ascending Dose Trial of ATI-450, an Investigational Oral MK2 Inhibitor

Aclaris Therapeutics, Inc. announced positive results from ATI-450-PKPD-101, a single ascending dose and multiple ascending dose Phase 1 clinical trial of the investigational compound ATI-450. [Aclaris Therapeutics, Inc.] Press Release

Astellas Strengthens Immuno-Oncology Pipeline with Acquisition of Xyphos Biosciences, Inc.

Astellas Pharma Inc. and Xyphos Biosciences, Inc. announced that Astellas has acquired Xyphos. [Astellas Pharma Inc.] Press Release

Government Call for Science ‘Weirdos’ Prompts Caution from Researchers

Researchers have reacted with surprise and caution to a bizarrely worded job advertisement posted by a senior UK government adviser. The notice calls for scientists, mathematicians and “super-talented weirdos” to work for the prime minister and to help make “rapid progress with long-term problems”, and cites several scientific papers. [Nature News] Editorial

UK Group Tackles Reproducibility in Research

Last month, ten UK universities became part of the UK Reproducibility Network, joining a network that already includes stakeholders such as the Academy of Medical Sciences, Research Libraries UK, the National Institute for Biological Standards and Control, journals including Nature and PLOS, and local networks of researchers. [The Scientist] Editorial

NEW Keystone Symposia: T Cell Memory
March 1-5, 2020
Banff, Alberta, Canada

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NEW Postdoctoral Researcher – Immuno-Oncology (Essen University Hospital)

NEW Postdoctoral Scientist – Granuloma (Texas Biomedical Research Institute)

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

NEW Faculty Position – Ion Channels and Immunology (NYU School of Medicine)

NEW Biologist – Aging (NIH National Institute on Aging)

Postdoctoral Fellowship – Immunology (Stanford University)

Postdoctoral Research Associate – Immunity (University of Illinois at Chicago)

Tenure Track Position – Genetics/Genomics/Pharmacogenomics of Immune Function in Disease (University of Kentucky)

Postdoctoral Scholar Position – Molecular Biology, Immunology and Synthetic Biology (University of California, Irvine)

Postdoctoral Fellow Positions – Computational Immunology/Biology (Memorial Sloan Kettering Cancer Center)

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