Immune Regulation News Volume 7.31 | Aug 21 2015

Humanized Mice Reveal Differential Immunogenicity of Cells Derived from Autologous Induced Pluripotent Stem Cells
Using a humanized mouse model reconstituted with a functional human immune system, investigators demonstrated that most teratomas formed by autologous integration-free human induced pluripotent stem cells (hiPSCs) exhibit local infiltration of antigen-specific T cells and associated tissue necrosis, indicating immune rejection of certain hiPSC-derived cells. [Cell Stem Cell] Abstract | Graphical Abstract | Press Release

Spatiotemporally Distinct Interactions with Dendritic Cell Subsets Facilitates CD4⁺ and CD8⁺ T Cell Activation to Localized Viral Infection
Using a cutaneous herpes simplex virus infection model combined with intravital 2-photon imaging of the draining lymph node to concurrently visualize pathogen-specific CD4⁺ and CD8⁺ T cells, scientists found that early priming of CD4⁺ T cells involved clustering with migratory skin dendritic cells. [Immunity]
Abstract | Graphical Abstract | Press Release | Video

T_H2 and T_H17 Inflammatory Pathways Are Reciprocally Regulated in Asthma
Investigators demonstrated that asthma can be divided into three immunological clusters: T_H2-high, T_H17-high, and T_H2/17-low. Moreover, neutralizing one signature promoted the other in a mouse model of asthma. [Sci Transl Med] Abstract | Press Release

Breaking Immune Tolerance by Targeting Foxp3⁺ Regulatory T Cells Mitigates Alzheimer’s Disease Pathology
Scientists showed, using the 5XFAD Alzheimer’s disease mouse model, that transient depletion of Foxp3⁺ regulatory T cells, or pharmacological inhibition of their activity, is followed by amyloid-β plaque clearance, mitigation of the neuroinflammatory response and reversal of cognitive decline. [Nat Commun] Full Article

IL-22 Regulates Lymphoid Chemokine Production and Assembly of Tertiary Lymphoid Organs
Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, investigators demonstrated that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. [Proc Natl Acad Sci USA] Abstract | Full Article

IRF5 Controls Both Acute and Chronic Inflammation
Researchers explored the role of IFN regulatory factor 5 (IRF5) in models of acute inflammation, including antigen-induced inflammatory arthritis and lung injury, both involving an extensive influx of neutrophils. Mice lacking IRF5 accumulated far fewer neutrophils at the site of inflammation due to the reduced levels of chemokines important for neutrophil recruitment, such as the chemokine ligand 1. [Proc Natl Acad Sci USA] Abstract

Galectin-8 Promotes Regulatory T-Cell Differentiation by Modulating IL-2 and TGFβ Signaling
Investigators report that galectin (Gal)-8 promotes the polyclonal differentiation of primary mouse regulatory T (Treg) cells in vitro. Investigation of the mechanism by which Gal-8 promotes Treg conversion revealed that Gal-8 activates transforming growth factor-β (TGFβ) signaling and promotes sustained interleukin (IL)-2R signaling. [Immunol Cell Biol] Abstract

The Breast Tumor Microenvironment Alters the Phenotype and Function of Natural Killer Cells
Scientists examined the developmental state of natural killer (NK) cells from polyoma middle T antigen transgenic mouse breast tumors. To delineate whether the tumor microenvironment directly alters NK cells, they adoptively transferred labeled NK cells and followed their activation status in both the spleen and the tumor. [Cell Mol Immunol] Abstract

Ligation of CD180 Inhibits IFN-α Signaling in a Lyn-PI3K-BTK-Dependent Manner in B Cells
Investigators explored the effect of CD180 on regulating the activation of interferon-α (IFN-α) signaling in B cells. Notably, ligation of CD180 significantly inhibited the IFN-α-induced phosphorylation of signal transducer and activator of transcription 2 and expression of IFN-stimulated genes in a Lyn-PI3K-BTK-dependent manner in vitro. [Cell Mol Immunol] Abstract

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$52 Million NIH Grant Advances Clinical and Translational Research at UC San Diego
The Clinical and Translational Research Institute at University of California, San Diego has received a five-year Clinical and Translational Science Award for approximately $52 million from the National Center for Advancing Translational Science, part of the National Institutes of Health (NIH). [UC San Diego Health] Press Release

Esperite Acquires Patent to Use MSC-Derived Exosomes for Broad Applications in Immunology
Esperite has acquired the full rights of a broad international patent enabling MSC-derived exosomes use in treatment of inflammatory and autoimmune diseases. Esperite is positioned to spearhead advances in treatment for graft versus host disease after solid organ and cell transplantations, Crohn’s disease, arthritis, multiple sclerosis, cystic fibrosis, stroke, traumatic brain and spinal cord injury, newborn encephalopathy, and type 1 diabetes among others. [Esperite N.V.] Press Release

Novartis Acquires All Remaining Rights to GSK’s Ofatumumab to Develop Treatments for MS and Other Autoimmune Indications
Novartis announced that it has entered into an agreement to acquire all remaining rights to Ofatumumab from GlaxoSmithKline plc (GSK). Ofatumumab, a fully human monoclonal antibody which targets CD20, is being developed for relapsing remitting multiple sclerosis and other autoimmune indications. [Novartis AG] Press Release

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Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Research Fellow – Development and Pathogenesis of Pancreatic Cancer (University College London)

Senior Research Technician (Qu Biologics Inc.)

Postdoctoral Fellow – Immunology (The Henry M. Jackson Foundation)

Postdoctoral Fellow – Biotechnology (Qu Biologics Inc.)

Harry Eagle Scholar Awards for Postdoctoral Candidates (Albert Einstein College of Medicine of Yeshiva University)

Postdoctoral Positions – Cancer Research (Rutgers University)

Research Associate – Cell Biology (Editas Medicine)

Senior Research Associate – CRISPR-Based Therapeutics (Editas Medicine)

Research Assistant – Immunotherapy for HIV Infection (California Institute of Technology)

PhD Studentship – Veterinary and Animal Sciences (University of Milan)

Postdoctoral Researcher – Tumorigenesis and Immune Response (Nationwide Children Hospital-Ohio)

Senior Scientist – Immunology (Valera LLC)

Postdoctoral Fellow – Immune Reconstitution in Hematopoietic Stem Cell Transplantation (Stanford University)

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