Immune Regulation News Volume 10.29 | Aug 3 2018

TOP STORY

LKB1 Deficiency in T Cells Promotes the Development of Gastrointestinal Polyposis

Scientists report that heterozygous deletion of Stk11 in T cells (LT^het mice) was sufficient to promote gastrointestinal polyposis. Polyps from LT^het mice, Stk11^+/− mice, and human Peutz-Jeghers syndrome patients displayed hallmarks of chronic inflammation, marked by inflammatory immune-cell infiltration, signal transducer and activator of transcription 3 activation, and increased expression of inflammatory factors associated with cancer progression. [Science] Abstract | Press Release

(Ranked by impact factor of the journal)

Tle Corepressors Are Differentially Partitioned to Instruct CD8⁺ T Cell Lineage Choice and Identity

Tle3 bound to Runx-occupied Thpok silencer, in post-selection double-positive thymocytes to prevent excessive ThPOK induction and in mature CD8⁺ T cells to silence Thpok expression. [J Exp Med] Abstract | Graphical Abstract

IKZF1 Enhances Immune Infiltrate Recruitment in Solid Tumors and Susceptibility to Immunotherapy

Investigators showed that overexpression of the master regulator IKZF1 led to enhanced immune infiltrate recruitment and tumor sensitivity to PD1 and CTLA4 inhibitors in several tumors that normally lack IKZF1 expression. [Cell Syst] Abstract | Press Release | Graphical Abstract

Timed Regulation of 3BP2 Induction Is Critical for Sustaining CD8⁺ T Cell Expansion and Differentiation

Researchers demonstrated that 3BP2 was recruited in cytoplasmic microclusters and nucleated a signaling complex that facilitated MHC:peptide-independent activation of signaling pathways downstream of the TCR. [Cell Rep] Full Article | Graphical Abstract

Autophagy Is a Tolerance-Avoidance Mechanism that Modulates TCR-Mediated Signaling and Cell Metabolism to Prevent Induction of T Cell Anergy

Investigators identified autophagy as a tolerance-avoidance mechanism. They showed that inhibition of autophagy during CD4⁺ T cell activation induced a long-lasting state of hypo-responsiveness that was accompanied by the expression of an anergic gene signature. [Cell Rep] Full Article | Graphical Abstract

Notch Ligand Delta-Like 4 Induces Epigenetic Regulation of Treg Cell Differentiation and Function in Viral Infection

The authors report that delta-like ligand 4 (DLL4) dynamically increased histone H3 at lysine 4 methylation around the Foxp3 locus that was dependent upon upregulated SET and MYDN domain containing protein 3 (SMYD3). DLL4 promoted Smyd3 through the canonical Notch pathway in iT_reg differentiation. [Mucosal Immunol] Abstract

Rsad2 Is Necessary for Mouse Dendritic Cell Maturation via the IRF7-Mediated Signaling Pathway

Radical S-adenosyl methionine domain containing 2 (Rsad2) was induced at high levels in LPS-stimulated mature dendritic cells (mDCs) and mDC function was markedly attenuated under conditions of Rsad2 knockdown. Moreover, Rsad2 was necessary for mDC maturation via the IRF7-mediated signaling pathway. [Cell Death Dis] Full Article

In Vivo Neutralization of the Protagonist Role of Macrophages during the Chronic Inflammatory Stage of Huntington’s Disease

The authors showed that peripheral and CNS immune system activity increased with disease progression in Huntington’s disease mouse models and defined the phenotype of the immune response. [Sci Rep] Full Article

The Protective Role of Human Ghrelin in Sepsis: Restoration of CD4 T Cell Proliferation

Treatment with ghrelin restored the loss of CD4 T cells by increasing their proliferation in septic mice. The expression of cyclin D1 and B1 was significantly increased, while the expression of p57 was decreased in ghrelin-treated mice compared to vehicle-treated mice in sepsis. [PLoS One] Full Article

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CD4⁺ T Cell Help in Cancer Immunology and Immunotherapy

The authors highlight the cellular dynamics and membrane receptors that mediate CD4⁺ T cell help and the molecular mechanisms of the enhanced antitumour activity of cytotoxic T lymphocytes (CTLs). They outline how deficient CD4⁺ T cell help reduces the response of CTLs and how maximizing CD4⁺ T cell help can improve outcomes in cancer immunotherapy strategies. [Nat Rev Immunol] Abstract

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ABL Bio and I-Mab Biopharma Announce Global Collaboration on Innovative Bispecific Antibodies

ABL Bio Corporation and I-Mab Biopharma jointly announced that the two companies had entered into a global strategic partnering agreement. [ABL Bio Corporation (PR Newswire Association LLC.)] Press Release

HiFiBiO Therapeutics Signs Multi-Target Antibody Discovery Agreement with Takeda

HiFiBiO Therapeutics announced a multi-target agreement with Takeda Pharmaceutical Company Limited to enable the discovery of breakthrough antibody therapies to potentially treat various gastrointestinal diseases, cancers and other disorders. [HiFiBiO Therapeutics] Press Release

Arcus Biosciences Announces Initiation of Phase I Trial for AB154, Its Anti-TIGIT Antibody

Arcus Biosciences, Inc. announced that it has received regulatory approval to initiate its Phase I trial for AB154, its anti-TIGIT antibody, and expects to start dosing patients shortly. AB154 is the company’s third product candidate to enter clinical development. [Arcus Biosciences, Inc.] Press Release

Gigantic Review of German Science Recommends More Data and Diversity

Germany’s largest research organization is funding top-notch science, but it needs to employ more foreign and female researchers — and it is failing to leverage ‘big data’, such as electronic medical records. [Nature News] Editorial

Brexit Preparedness: EMA to Further Temporarily Scale Back and Suspend Activities

The European Medicines Agency (EMA) will launch the next phase of its business continuity plan on 1 October 2018 at the latest. This will allow the Agency to safeguard core activities related to the evaluation and supervision of medicines, while it has to intensify its preparations for the physical move to Amsterdam in March 2019 and cope with significant staff loss. [European Medicines Agency] Press Release

March of Dimes Abruptly Scales Back Research Funding

March of Dimes, the 80-year-old nonprofit organization that has funded pioneering studies on premature birth, infant mortality, and birth defects, is abruptly scaling back its investment in research amid financial struggles—catching scientists by surprise. [ScienceInsider] Editorial

NEW Keystone Symposia: Myeloid Cells
February 24-28, 2019
Santa Fe, New Mexico, United States

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

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

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Research Assistant – Immune Response (University of Cambridge)

Postdoctoral Fellow – Immunotherapy (California Institute for Biomedical Research)

Postdoctoral Researcher – T Cell Biology (Washington University School of Medicine)

Professorship – Molecular Immune Regulation (Kiel University)

Postdoctoral Fellowships – Immunometabolism (St. Jude Children’s Research Hospital)

Assistant/Associate Professor – Immunology (University of Massachusetts)

PhD Student – Cellular Immunotherapy (Glycostem Therapeutics)

Assistant, Associate, or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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