Human Immunology News Volume 5.41 | Oct 17 2017

TOP STORY

A Cautionary Tale

Scientists have elucidated the mechanism by which human cells induce inflammation upon detection of cytoplasmic DNA. Notably, the signal network involved differs from that used in the same context in mice. [Press release from Ludwig-Maximilians-Universität discussing online prepublication in Cell] Press Release | Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Molecular and Functional Characterization of Lymphoid Progenitor Subsets Reveals a Bipartite Architecture of Human Lymphopoiesis

Combining molecular analyses with in vitro and in vivo functional assays, investigators demonstrated that CD127^– and CD127⁺ early lymphoid progenitors emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials. [Immunity] Full Article | Graphical Abstract

Epidermal Growth Factor Receptor Expression Licenses Type-2 Helper T Cells to Function in a T Cell Receptor-Independent Fashion

Researchers showed that, as a prerequisite for IL-33-induced IL-13 secretion, type-2 helper T cells required the expression of the epidermal growth factor receptor (EGFR) and of its ligand, amphiregulin, for the formation of a signaling complex between T1/ST2 and EGFR. [Immunity] Full Article | Graphical Abstract

An Analysis of IL-36 Signature Genes and Individuals with IL1RL2 Knockout Mutations Validates IL-36 as a Psoriasis Therapeutic Target

Scientists defined the genes that are induced by IL-36 cytokines in primary human keratinocytes. They investigated the impact of in vivo and ex vivo IL-36 receptor blockade using a neutralizing antibody or a recombinant antagonist. Finally, they explored the potential safety profile associated with IL-36 blockade by phenotyping 12 individuals carrying knockout mutations of the IL-36 receptor gene. [Sci Transl Med] Abstract

NMI and IFP35 Serve as Proinflammatory DAMPs during Cellular Infection and Injury

Investigators report that two molecules, N-myc and STAT interactor (NMI) and interferon-induced protein 35 (IFP35), acted as damage-associated molecular patterns and were released by activated macrophages during lipopolysaccharide-induced septic shock or acetaminophen-induced liver injury. They showed that extracellular NMI and IFP35 activate macrophages to release proinflammatory cytokines by activating nuclear factor-κB through the toll-like receptor 4 pathway. [Nat Commun] Full Article

BAD-LAMP Controls TLR9 Trafficking and Signaling in Human Plasmacytoid Dendritic Cells

Scientists showed that BAD-LAMP controls toll-like receptor (TLR) 9 trafficking to LAMP1⁺ late endosomes in human plasmacytoid dendritic cells, leading to NF-κB activation and TNF production upon DNA detection. BAD-LAMP-silencing enhanced TLR9 retention in a compartment and consequent downstream signaling events. [Nat Commun] Full Article

Gut Dysbiosis Breaks Immunological Tolerance toward the Central Nervous System during Young Adulthood

Researchers investigated the effects of age and gut dysbiosis on the development of central nervous system autoimmunity in humanized transgenic mice expressing the multiple sclerosis (MS)-associated MHC class II gene, HLA-DR2a, and T-cell receptor genes specific for MBP87-99/DR2a that were derived from an MS patient. [Proc Natl Acad Sci USA] Abstract

CAR T Therapy Targeting ICAM-1 Eliminates Advanced Human Thyroid Tumors

Scientists developed a third-generation CAR targeting ICAM-1 to leverage adoptive T cell therapy as a new treatment modality. ICAM-1 CAR T cells demonstrated robust and specific killing of papillary thyroid cancer and anaplastic thyroid cancer cell lines in vitro. [Clin Cancer Res] Abstract

Resveratrol Stimulates the Metabolic Reprogramming of Human CD4⁺ T Cells to Enhance Effector Function

Investigators found that at high concentrations of resveratrol, human CD4⁺ T cells showed defective antigen receptor signaling and arrest at the G₁ stage of the cell cycle, whereas at low concentrations, cells were readily activated and exhibited enhanced Sirt1 deacetylase activity. [Sci Signal] Abstract

Cibinetide Dampens Innate Immune Cell Functions Thus Ameliorating the Course of Experimental Colitis

Erythropoietin receptor (EPOR) homodimers signal to promote the maturation of erythroid progenitor cells. In other cell types, including immune cells, EPOR and the β-common receptor (CD131) form heteromers, and exert tissue protective effects. Experiments using LPS-activated primary macrophages revealed that the anti-inflammatory effects of cibinetide were dependent on CD131 and JAK2 functionality and were mediated via inhibition of NF-κB subunit p65 activity. [Sci Rep] Full Article

Infusion of Autograft Natural Killer Cell/CD14⁺HLA-DR^DIM Cell Ratio Predicts Survival in Lymphoma Post Autologous Stem Cell Transplantation

The authors investigated whether the autograft natural killer cells (A-NKC)/A-CD14⁺HLA-DR^DIM ratio predicts survival in non-Hodgkin’s lymphoma. Multivariate analysis revealed that A-NKC/A-CD14⁺HLA-DR^DIM ratio was an independent predictor for PFS and overall survival. [Bone Marrow Transplant] Abstract

Gefitinib Inhibits M2-Like Polarization of Tumor-Associated Macrophages in Lewis Lung Cancer by Targeting the STAT6 Signaling Pathway

Researchers investigated the relevance of macrophage polarization and the antitumor effect of gefitinib in Lewis lung cancer (LLC) in vitro and in vivo. A small concentration of gefitinib significantly inhibited IL-13-induced M2-like polarization of macrophages, evidenced by the decreased expression of the M2 surface markers CD206 and CD163, down-regulation of specific M2-marker genes, as well as inhibition of M2-like macrophage-mediated invasion and migration of LLC cells. [Acta Pharmacol Sin] Abstract

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Monocyte-Macrophages and T Cells in Atherosclerosis

The adaptive immune response is regulated primarily by mechanisms that affect the balance between regulatory and effector T cells. Mechanisms related to cellular cholesterol, phenotypic plasticity, metabolism, and aging play key roles in affecting these responses. Scientists review select topics that shed light on these processes and suggest new treatment strategies. [Immunity] Full Article

Emerging Principles from the Clinical Application of Chimeric Antigen Receptor (CAR) T Cell Therapies for B Cell Malignancies

Gene-engineered T cell therapies are soon to be FDA approved for at least two types of B cell malignancies in pediatric and adult patients, in the form of CD19 targeted CAR T cell therapy. The authors review the “lessons learned” from the pre-clinical and human experience with CAR T cell therapy. [Stem Cells] Abstract

Visit our reviews page to see a complete list of reviews in the human immunology research field.

Omeros Announces Upcoming Presentation of Clinical OMS721 Data

Omeros Corporation announced that data will be presented from the company’s Phase II clinical trial of OMS721, Omeros’ lead human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2, for the treatment of thrombotic microangiopathies. [Press release from Omeros Corporation discussing research to be presented at the 43^rd edition of the European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting, Granada] Press Release

Infinity Announces IPI-549 Late-Breaking Presentation

Infinity Pharmaceuticals, Inc. announced that an abstract describing new data for IPI-549, an orally administered immuno-oncology development candidate that selectively inhibits phosphoinositide-3-kinase gamma, has been selected as a late-breaking presentation during an oral session. [Press release from Infinity Pharmaceuticals, Inc. discussing research to be presented at the 2017 Society for Immunotherapy of Cancer (SITC) Annual Meeting, National Harbor] Press Release

Alpine Immune Sciences Announces Upcoming Scientific Presentations

Alpine Immune Sciences, Inc., a leading immunotherapy company focused on developing treatments for autoimmune/inflammatory diseases and cancer, announced planned poster presentations highlighting recent data at scientific meetings. [Press release from Alpine Immune Sciences, Inc. discussing research to be presented at various conferences] Press Release

Dana-Farber Cancer Institute Joins the Parker Institute for Cancer Immunotherapy

The Parker Institute for Cancer Immunotherapy announced that researchers at Dana-Farber Cancer Institute have joined its network. Dana-Farber is a leader in cancer research and brings a team of experts who will collaborate with Parker Institute investigators to enhance and expand research projects and clinical trials. [Dana-Farber Cancer Institute] Press Release

Aimmune Therapeutics Announces Clinical Collaboration to Study AR101 with Regeneron and Sanofi’s Dupilumab for Peanut Allergy

Aimmune Therapeutics, Inc. announced a clinical collaboration with Regeneron and its strategic alliance collaborator Sanofi to study AR101 treatment with adjunctive dupilumab in peanut-allergic patients in a Phase II clinical trial. [Aimmune Therapeutics, Inc.] Press Release

VLP Therapeutics Announces Phase I SBIR Grant Award from National Cancer Institute

VLP Therapeutics, LLC announced the receipt of a Phase I grant from the National Cancer Institute under auspices of the Small Business Innovation Research (SBIR) program of the National Institutes of Health. The $298,729 grant under the Award Number R43CA217445 is focused on “the development of a novel Virus-Like Particle vaccine-based cancer immunotherapy targeting PD-L1” and will also explore broader immune checkpoint inhibition mechanisms. [VLP Therapeutics, LLC] Press Release

Regen BioPharma, Inc. Researchers Capitalize on Key Structure in Compounds that Activate Checkpoint NR2F6 for the Potential Treatment of Autoimmune Diseases

Regen BioPharma Inc. believes it has taken full advantage of its recent prior discovery in developing small molecule drugs that activate NR2F6. The company recently reported that it identified key structural elements in small molecules that make them active and specific towards the NR2F6 target. [Regen BioPharma Inc. (PR Newswire Association LLC.)] Press Release

Japanese Research Leaders Warn about National Science Decline

As Japan heads towards a national election, scientific leaders worry that the outcome will do little to address long-standing concerns about the country’s deteriorating research landscape. They say that a decline in funding and a shift away from basic research has undermined Japan’s capacity to compete against both established scientific powerhouses and emerging ones such as China. [Nature News] Editorial

Trump’s UNESCO Exit Draws Critics, but Will Have Little Immediate Impact

To the dismay of many researchers, the U.S. government announced that it would formally withdraw from the United Nations Educational, Scientific and Cultural Organization (UNESCO) based in Paris. The decision—which is not expected to cause major disruptions in UNESCO’s science programs—comes roughly six years after the United States stopped contributing funds to the organization because of its recognition of Palestine, and four years after the United States lost its UNESCO voting rights. [ScienceInsider] Editorial

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