Immune Regulation News Volume 8.39 | Oct 21 2016

TOP STORY

The Integrin LFA-1 Controls T Follicular Helper Cell Generation and Maintenance

Investigators showed that T follicular helper (Tfh) cells expressed a highly active form of leukocyte function-associated antigen-1 (LFA-1) that was required for their survival within the germinal center niche. In addition, LFA-1 promoted expression of Bcl-6, a transcriptional repressor critical for Tfh cell differentiation, and inhibition of LFA-1 abolished Tfh cell generation and prevented protective humoral immunity to intestinal helminth infection. [Immunity] Abstract | Graphical Abstract

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A Tissue Checkpoint Regulates Type 2 Immunity

Scientists found that tissue group 2 innate lymphoid cells and type 2 helper T cells differentiated independently but shared overlapping effector function programs that were mediated by exposure to the tissue-derived cytokines interleukin 25, IL-33 and thymic stromal lymphopoietin. [Nat Immunol] Abstract

DR3 Signaling Modulates the Function of Foxp3⁺ Regulatory T Cells and the Severity of Acute Graft versus Host Disease

Researchers comprehensively analyzed the immunophenotype of regulatory T cells (Tregs) after DR3 signal activation, demonstrating that DR3 activated Treg (DR3-Treg) had an activated/mature phenotype. Furthermore, the CD25⁺Foxp3⁺ subpopulation in DR3-Treg showed stronger suppressive effects in vivo. [Blood] Abstract

A Switch in Regulatory T Cells through Farm-Exposure during Immune Maturation in Childhood

The authors investigated the critical time window of the “asthma-protective” farm effect via regulatory T-cells during childhood immune maturation. [Allergy] Abstract

A Critical Role for IRF5 in Regulating Allergic Airway Inflammation

The authors used genetic ablation, adenoviral vector-driven overexpression, and adoptive transfer approaches to interrogate the role of interferon regulatory factor 5 (IRF5) in pulmonary immunity and during challenge with the aeroallergen, house dust mite. [Mucosal Immunol] Abstract

Unique B7-H1 Expression on Masticatory Mucosae in the Oral Cavity and Trans-Coinhibition by B7-H1-Expressing Keratinocytes Regulating CD4⁺ T Cell-Mediated Mucosal Tissue Inflammation

The blocking of keratinocyte (KC)-associated B7 homolog 1 (B7-H1) or the lack of programmed cell death-1 on tissue effector CD4⁺ T cells in mice lacking B7-H1 on immune cells drastically exacerbated the tissue inflammation induced by topical OVA painting as an exogenous antigen, indicating direct interaction with KCs and CD4⁺ T cells. [Mucosal Immunol] Abstract

ICOS⁺ Foxp3⁺ TILs in Gastric Cancer Are Prognostic Markers and Effector Regulatory T Cells Associated with Helicobacter pylori

In tumor-infiltrating lymphocytes (TILs), TCR-inducible costimulatory receptor (ICOS)⁺ Foxp3⁺ CD4⁺ T cells were abundantly observed in the late stages of gastric cancer. ICOS⁺ CD4⁺ TILs exhibited the ability to produce IL-10, but not IFNγ, TNF, or IL-17 and also to suppress the proliferation of CFSE-labeled responder CD8⁺ T cells. [Int J Cancer] Abstract

Regulatory T Cells, Especially ICOS⁺ FOXP3⁺ Regulatory T Cells, Are Increased in the Hepatocellular Carcinoma Microenvironment and Predict Reduced Survival

Scientists analyzed the prognostic value of tumor-infiltrating lymphocytes, especially regulatory T cells, in hepatocellular carcinoma patients. [Sci Rep] Full Article

A Rare Subset of Skin-Tropic Regulatory T Cells Expressing Il10/Gzmb Inhibits the Cutaneous Immune Response

Researchers investigated single-cell gene expression heterogeneity in regulatory T cells (Tregs) from the draining lymph node of inflamed skin in a contact hypersensitivity model. The immunosuppressive genes Ctla4 and Tgfb1 were expressed in the majority of Tregs. [Sci Rep] Full Article

Decline of miR-124 in Myeloid Cells Promotes Regulatory T Cell Development in HCV Infection

The authors have recently shown marked expansion of myeloid-derived suppressor cells (MDSCs) that promote regulatory T cell development in patients with chronic hepatitis C virus (HCV) infection. Here they investigated whether the HCV-induced expansion of MDSCs and Tregs is regulated by a miRNA-mediated mechanism. [Immunology] Abstract

Costunolide, a Sesquiterpene Lactone, Inhibits the Differentiation of Pro-Inflammatory CD4⁺ T Cells through the Modulation of Mitogen-Activated Protein Kinases

Researchers investigated the effects of costunolide, a plant-derived natural compound with an anti-inflammatory activity, in regulating T helper (Th) cells and the underlying mechanisms. Costunolide significantly decreased cell populations of differentiated Th1, Th2, and Th17 subsets under Th subset-polarizing conditions, while exerting statistically negligible effects on Treg cell differentiation. [Int Immunopharmacol] Abstract

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Dendritic Cells in Human Lung Disease: Recent Advances

Though an extensive body of literature has documented the role that dendritic cells (DCs) play in experimental models of lung disease, this review will highlight recent advances in our understanding of DC function in human disease, including asthma, COPD, anti-microbial immunity and lung cancer. [Chest] Full Article

The Biological Function and Significance of CD74 in Immune Diseases

CD74 plays important roles in many inflammatory diseases, such as liver fibrosis, type I diabetes, systemic lupus erythematosus, and Alzheimer disease. The authors focus on the immunological functions of CD74 molecules and its roles in immune-relevant disorders. [Inflamm Res] Abstract

Tissue Engineering Approaches to Modulate the Inflammatory Milieu following Spinal Cord Injury

The authors summarize the strategies that have been developed to modulate the immune response towards an anti-inflammatory environment that is permissive to the regeneration of neurons, glia, and parenchyma. [Cells Tissues Organs] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation research field.

Cantargia to Present New Data from Preclinical Studies with CAN04 in Non-Small Cell Lung Cancer

Cantargia AB will be presenting data from preclinical studies in non-small cell lung cancer, where the product candidate CAN04, a humanized antibody against the IL1RAP target molecule, has been investigated. [Press release from Cantargia AB discussing research presented at the Protein & Antibody Engineering Summit (PEGS), Lisbon] Press Release

Anti-MUC1 MAb AR20.5 Induces Specific Cell Mediated Immune Response to MUC1 Antigen in Pre-Clinical Pancreatic Cancer Model

OncoQuest Inc. announced positive results from its pre-clinical pharmacology studies using its Anti-MUC1 antibody, MAb AR20.5, against pancreatic cancer in a human MUC1 expressing transgenic mouse model. [Press release from OncoQuest Inc. (PR Newswire Association LLC.) discussing research to be presented at the American Association for Cancer Research (AACR) Special Conference on Tumor Immunology and Immunotherapy, Boston] Press Release

Omeros Announces Positive Data from OMS721 Phase II Trial in Patients with Stem Cell Transplant-Associated Thrombotic Microangiopathy

Omeros Corporation announced positive results in patients with hematopoietic stem cell transplant-associated thrombotic microangiopathy from the company’s Phase II clinical trial of OMS721 in TMAs, with clinically meaningful improvement in measures of red blood cell destruction, specifically lactate dehydrogenase and haptoglobin levels. [Omeros Corporation] Press Release

CStone Pharmaceuticals’ PD-L1 Monoclonal Antibody IND Has Been Formally Accepted by the CFDA

CStone Pharmaceuticals announced that, following the successful site inspection by the Jiangsu FDA for its recombinant anti PD-L1 monoclonal antibody, the CFDA has recently accepted the submission of WBP3155’s IND. [CStone Pharmaceuticals (PR Newswire Association LLC.)] Press Release

Debiopharm International SA Announces Clinical Collaboration with the Merck-Pfizer Alliance in Cancer Immunotherapy

Debiopharm International announced that it has entered into a collaboration agreement with Merck and Pfizer to evaluate Debio 1143, an oral, small molecule inhibitor of IAPs (inhibitor of apoptosis proteins), in combination with avelumab, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in patients with advanced or metastatic non-small cell lung cancer. [Debiopharm International SA] Press Release

Europe’s Drug Regulator Opens Vaults of Clinical-Trials Data

In a move lauded as a landmark for transparency in medical science, the London-based European Medicines Agency (EMA) has begun to publish details of the full clinical-trial data that it receives from pharmaceutical companies. The disclosures make the EMA the first major drug regulatory agency to publish the warts-and-all results of clinical investigations that drug developers submit when they apply for the agency’s approval to market medicines in the EU. [Nature News] Editorial

Reports of ‘Three-Parent Babies’ Multiply

Claims of infants created using mitochondrial-replacement techniques stir scientific and ethical debate. [Nature News] Editorial

How Republicans Reshaped the House Science Committee

Lamar Smith has made his mark on science. As chairman of the US House Committee on Science, Space, and Technology, the Texas Republican has launched dozens of investigations into alleged wrongdoing by scientists, environmental groups and government officials. And he shows no signs of slowing down. [Nature News] Editorial

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February 2-4, 2017
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NEW Senior/Advanced Research Assistant – CRISPR/Cas9 Screens in Immune Cells (Wellcome Trust Sanger Institute)

NEW Scientist – T Cells in Autoimmune Diabetes (Helmholtz Zentrum Munchen)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Position – Mucosal Immunology/Neuro-Immune Interaction (KU Leuven)

Postdoctoral Position – Immunology (Klinikum der Universität München)

Faculty Positions – Immunology (Ohio State University)

Faculty Position – Immunogen Development and Evaluation (Fred Hutchinson Cancer Research Center)

Research Associate – Cellular Therapy (California Institute for Biomedical Research)

Director – Immunobiology and Microbial Pathogenesis (The Salk Institute for Biological Studies)

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

Postdoctoral Fellow – Immunology (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Molecular Immunology (University of California, San Diego)

Chair – Medical Biology (Masaryk University)

Postdoctoral Fellow Position – Stem Cell Biology & Immunology (Toronto General Research Institute & McEwen Centre for Regenerative Medicine)

Postdoctoral Fellow – Genomics and Human Immunity (The Jackson Laboratory)

Faculty Position – Immunology (Vanderbilt University Medical Center)

Postdoctoral Fellow – Mucosal Immunology (University of Utah)

Postdoctoral Research Scientist (National Taiwan University)

Postdoctoral Research – Fellow Thymic and Immune Regeneration (Fred Hutchinson Cancer Research Center)

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