Immune Regulation News Volume 10.26 | Jul 13 2018

TOP STORY

Maintenance of CD4 T Cell Fitness through Regulation of Foxo1

Scientists used a system in which Foxo1 transcription-factor activity, which is normally terminated upon cell activation, cannot be silenced, and they showed that enforcing Foxo1 activity disrupts homeostasis of CD4 conventional and regulatory T cells. [Nat Immunol] Abstract

(Ranked by impact factor of the journal)

Translational Repression of Pre-Formed Cytokine-Encoding mRNA Prevents Chronic Activation of Memory T Cells

Investigators found that protein production in memory T cells was blocked via a 3′ untranslated region (3′ UTR)-mediated process. Germline deletion of AU-rich elements in the Ifng-3′ UTR led to chronic cytokine production in memory T cells. [Nat Immunol] Abstract

Priming of Dendritic Cells by DNA-Containing Extracellular Vesicles from Activated T Cells through Antigen-Driven Contacts

Researchers showed that when antigen-bearing dendritic cells (DCs) contact T cells, DCs initiate anti-pathogenic programs. Signals of this interaction were transmitted from the T cell to the DC, through extracellular vesicles that contained genomic and mitochondrial DNA, to induce antiviral responses via the cGAS/STING cytosolic DNA-sensing pathway and expression of IRF3-dependent interferon regulated genes. [Nat Commun] Full Article

TCR Signal Strength Controls Thymic Differentiation of iNKT Cell Subsets

The authors showed that T cell antigen receptor (TCR) signal strength governed the development of invariant natural killer T (iNKT) cell subsets, with strong signaling promoting iNKT2 and iNKT17 development. [Nat Commun] Full Article

Antigen-Presenting Cell-Intrinsic PD-1 Neutralizes PD-L1 in cis to Attenuate PD-1 Signaling in T Cells

Researchers report that PD-1 is co-expressed with PD-1 ligand (PD-L1) on tumor cells and tumor-infiltrating antigen-presenting cells. Using reconstitution and cell culture assays, they demonstrated that the co-expressed PD-1 binds to PD-L1 in cis. [Cell Rep] Full Article | Press Release | Graphical Abstract

B-Cell-Intrinsic Type 1 Interferon Signaling Is Crucial for Loss of Tolerance and the Development of Autoreactive B Cells

Using a lupus model that allows for focused study of the antibody-forming cell (AFC) and germinal center (GC) responses, the authors showed that type 1 interferon signaling is crucial for autoreactive B cell development in the AFC and GC pathways. [Cell Rep] Full Article | Graphical Abstract

The Mouse Autonomic Nervous System Modulates Inflammation and Epithelial Renewal after Corneal Abrasion through the Activation of Distinct Local Macrophages

Scientists report that the manipulation of autonomic nervous system regulates inflammation and healing processes. The activation of sympathetic nerves inhibited re-epithelialization after corneal abrasion but increased the influx of neutrophils and the release of inflammatory cytokines. [Mucosal Immunol] Full Article

Metabolic Signaling Directs the Reciprocal Lineage Decisions of αβ and γδ T Cells

Investigators report that mechanistic target of rapamycin complex 1 couples microenvironmental cues with metabolic programs to orchestrate the reciprocal development of two fundamentally distinct T cell lineages, the αβ and γδ T cells. [Sci Signal] Full Article

The Costimulatory Molecule CD226 Signals through VAV1 to Amplify TCR Signals and Promote IL-17 Production by CD4⁺ T Cells

Engagement of CD226 induced the tyrosine phosphorylation of VAV1 and synergized with T cell receptor (TCR) signals to specifically enhance the production of interleukin-17 (IL-17) by primary human CD4⁺ T cells. [Sci Signal] Full Article

CCL5-Deficiency Enhances Intratumoral Infiltration of CD8⁺ T Cells in Colorectal Cancer

Researchers demonstrated that CCL5-deficiency delayed tumor growth and metastasis via facilitating CD8⁺ T cells to accumulate into tumor site in colorectal cancer mouse models. [Cell Death Dis] Full Article

Regulation and Biological Role of the Peptide/Histidine Transporter SLC15A3 in Toll-Like Receptor-Mediated Inflammatory Responses in Macrophage

Mouse peritoneal macrophages, mouse bone marrow-derived macrophages, the human acute monocytic leukemia cell line THP-1 and the human lung epithelial carcinoma cell line A549 were used to investigate the regulation and biological role of SLC15A3 in TLR-mediated inflammatory responses. [Cell Death Dis] Full Article

Autoantigen-Harboring Apoptotic Cells Hijack the Coinhibitory Pathway of T Cell Activation

Investigators found that apoptotic cells (ACs) specifically upregulated the coinhibitory ligand CD80 on macrophages. Conversely, ACs did not exhibit a robust regulation of the other coinhibitory ligands on macrophages or the costimulatory receptor CD28 on T cells. [Sci Rep] Full Article

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Delivery Strategies for Immune Checkpoint Blockade

The authors summarize strategies to increase the antitumor immunity, including the local and targeted delivery of checkpoint inhibitors, and a combination of different checkpoint inhibitors or with other therapeutic treatments. [Adv Healthc Mater] Abstract

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AbbVie Provides Update on Phase III Study of Ibrutinib (IMBRUVICA^®) in Blood Cancer Diffuse Large B-Cell Lymphoma (DLBCL) and Ongoing Ibrutinib Clinical Program

At conclusion of the study, data collected found that Ibrutinib plus the chemotherapy regimen, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), was not superior to R-CHOP alone, and that the study did not meet its primary endpoint of improving event-free survival in the targeted patient population. [AbbVie Inc.] Press Release

TxCell Exercises In-License Option to the University of British Columbia’s Intellectual Property Rights of the HLA-A2 CAR-Treg Program

TxCell SA announced it has exercised its exclusive option to in-license the intellectual property rights of one of its academic partners, the University of British Columbia, onto the HLA-A2 CAR-regulatory T cell (Treg) program. [TxCell SA] Press Release

Thomas Jefferson University and BioVaxys LLC Enter into Exclusive Worldwide License for Immunotherapeutic Cancer Vaccines

Thomas Jefferson University and BioVaxys LLC announced that they have entered into an exclusive worldwide license agreement for a technology comprising highly-targeted, patient-specific, immunotherapeutic vaccines to treat ovarian cancer, melanoma, and other solid tumor types. [Thomas Jefferson University (Business Wire, Inc.)] Press Release

It’s Time to Burst the Biomedical Bubble in UK Research

A new study calls for a rebalancing of research and innovation funding to better meet the UK’s economic, social and health needs. [The Guardian] Editorial

Chinese Researchers to Get More Autonomy Over Lab Spending

Chinese Premier Li Keqiang says the country will ease restrictive rules governing how research funds are used, and cut red tape for researchers. Revised rules are designed to help researchers focus on their work and compete with their counterparts globally. [Nature News] Editorial

UK Universities Fall Short on Reporting Misconduct Investigations

The United Kingdom should establish a committee to monitor efforts by the nation’s universities to properly conduct misconduct investigations, a parliamentary inquiry recommends. The guidance follows a new report released on 11 July, revealing that one in four UK universities does not comply with research integrity guidelines released six years ago. [Nature News] Editorial

NEW Keystone Symposia: Molecular Approaches to Vaccines and Immune Monitoring
February 10-14, 2019
Keystone, Colorado, United States

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NEW Postdoctoral Fellow – Immunotherapy (California Institute for Biomedical Research)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

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)

PhD Position – Characterization of the Immune Pathways that Stimulate Autoimmunity Caused By ADAR1 Deficiency (VIB)

PhD Student Positions – Immunology (Multiple Locations)

Postdoctoral Fellowship – Immunology (University of South Carolina)

Postdoctoral Position – Tumor Immunology and Cancer Immunotherapy (Vlaams Instituut voor Biotechnologie)

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

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