Volume 7.18 | May 22

Immune Regulation News 7.18 May 22, 2015
Immune Regulation News
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New Form of Interleukin-2 Could Be Fine-Tuned to Fight Disease
Scientists report the development of a new way to modify interleukin-2 (IL-2), a substance known as a cytokine that plays key roles in regulating immune system responses, in order to fine-tune its actions. Harnessing the action of IL-2 in a controllable fashion is of clinical interest with potential benefit in a range of situations, including transplantation and autoimmune disease. [Press release from the National Institutes of Health discussing publication in Immunity] Press Release | Full Article | Graphical Abstract
Free Poster: Quick Reference for Mouse Immune Cell Frequencies and Percentages
PUBLICATIONS (Ranked by impact factor of the journal)
Actin Depletion Initiates Events Leading to Granule Secretion at the Immunological Synapse
Cytotoxic T lymphocytes use polarized secretion to rapidly destroy virally infected and tumor cells. To understand the temporal relationships between key events leading to secretion, scientists used high-resolution 4D imaging. [Immunity] Full Article | Graphical Abstract | Press Release | Video

Intestinal Intraepithelial Lymphocyte Activation Promotes Innate Antiviral Resistance
Scientists showed that one of the most conspicuous impacts of activated intestinal intraepithelial lymphocytes on intestinal epithelial cells is the functional upregulation of antiviral interferon (IFN)-responsive genes, mediated by the collective actions of IFNs with other cytokines. [Nat Commun] Full Article

miR-125a Targets Effector Programs to Stabilize Treg-Mediated Immune Homeostasis
Scientists showed that miR-125a is downregulated in peripheral CD4+ T cells of human autoimmune diseases including systemic lupus erythematosus and Crohn’s disease, and relevant autoimmune mouse models. miR-125a stabilizes both the commitment and immunoregulatory capacity of Treg cells. [Nat Commun] Abstract

Circadian Control of Innate Immunity in Macrophages by miR-155 Targeting Bmal1
Researchers found that the clock in myeloid cells plays a role in lipopolysaccharide (LPS)-induced sepsis by altering NF-κB activity and the induction of the microRNA miR-155. LPS caused the repression of BMAL1 via the targeting of miR-155 to two seed sequences in the 3′-untranslated region of Bmal1. [Proc Natl Acad Sci USA] Abstract | Press Release

Th17 Cells Give Rise to Th1 Cells that Are Required for the Pathogenesis of Colitis
Using a Th17 transfer model of colitis, investigators found that IFN-γ–deficient Th17 cells retained an IL-17A+ phenotype and were unable to induce colitis in recipients. Development of disease required the transition of a subset of Th17 precursors to Th1-like cells and was contingent on the expression of both Stat4 and T-bet, but not the IL-12 or IFN-γ receptors. [Proc Natl Acad Sci USA] Abstract

Nuclear Matrix Protein SMAR1 Control Regulatory T-Cell Fate during Inflammatory Bowel Disease (IBD)
Investigators showed that SMAR1, a known transcription factor and tumor suppressor, is directly involved in maintaining regulatory T cell fate decision. T-cell-specific conditional knockdown of SMAR1 exhibits increased susceptibility towards inflammatory disorders, such as colitis. [Mucosal Immunol] Abstract

Modulation of Radiochemoimmunotherapy-Induced B16 Melanoma Cell Death by the Pan-Caspase Inhibitor zVAD-Fmk Induces Anti-Tumor Immunity in a HMGB1-, Nucleotide- and T-Cell-Dependent Manner
As hints exist that immune stimulation by hyperthermia (HT) augments the efficacy of melanoma therapies and that tumors can be sensitized for radiotherapy (RT) with zVAD-fmk, researchers investigated whether combinations of RT with dacarbazine and/or HT induce immunogenic melanoma cell death and how this is especially influenced by zVAD-fmk. [Cell Death Dis] Full Article

Microfluidic Squeezing for Intracellular Antigen Loading in Polyclonal B-Cells as Cellular Vaccines
Researchers utilized a microfluidic device that employs many parallel channels to pass single cells through narrow constrictions in high throughput. They demonstrated that both resting and activated B-cells process and present antigens delivered via mechano-poration exclusively to antigen-specific CD8+ T‑cells, and not CD4+ T‑cells. [Sci Rep] Full Article | Press Release

Vaccine-Induced aβ-Specific CD8+ T Cells Do Not Trigger Autoimmune Neuroinflammation in a Murine Model of Alzheimer’s Disease
Potential MHC-I-restricted Aβ-derived epitopes were first analyzed for their capacity to recruit functional CD8+ T cell responses in mouse models. Their impact on migration of CD8+ T cells into the brain parenchyma and potential induction of meningoencephalitis and/or neuronal damage was investigated upon vaccination in the APPPS1 mouse model of Alzheimer’s disease. [J Neuroinflammation] Abstract | Full Article

Suppression of Autoimmunity by CD5+ IL-10-Producing B Cells in Lupus-Prone Mice
Scientists showed that ablation of natural killer T cells with a CD1d knockout had no impact on either the suppression of lupus or the expansion of CD5+ B cells. On the other hand, suppressed mice had an expanded population of IL-10-producing B cells that predominantly localized to the CD5+CD1dlow compartment. [Genes Immun] Abstract

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Regulatory T Cell Identity: Formation and Maintenance
The authors review recent insights into the mechanisms that maintain T regulatory (Treg) cell stability and function, and place these findings within the broader understanding of mechanisms that establish Treg cell identity during development. They integrate emerging principles in Treg cell lineage maintenance with the mechanisms that allow Treg cells to sense and respond to varied inflammatory environments, and outline important areas of future inquiry in this context. [Trends Immunol] Abstract

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Wistar Receives $5.6 Million Grant Renewal from Wellcome Trust to Develop Drug against Cancers Caused by Epstein-Barr Virus
The Wistar Institute and London-based global charity Wellcome Trust announce that they have signed a follow-on funding agreement in support of ongoing research and development of a new class of drugs useful for treating cancers associated with Epstein-Barr virus. [The Wistar Institute] Press Release

OncoSec Medical and Massachusetts General Hospital to Evaluate Efficacy of Intratumoral Delivery of DNA-Based Interleukin-12
OncoSec Medical Inc. announced it has entered a sponsored research agreement with Massachusetts General Hospital. Under the agreement, researchers will evaluate the immunologic mechanisms underlying the anti-tumor effects of OncoSec’s clinical stage platform, ImmunoPulse™ IL-12, in a human papilloma virus tumor mouse model. [OncoSec Medical Inc.] Press Release

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National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW Cell Symposium: Cell Death and Immunity
November 8-10, 2015
Berkeley, United States

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NEW Head Stem Cells Immunotherapies Service Lab (NHS Blood and Transplant)

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

Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Process Facilitator (Opexa Therapeutics)

Postdoctoral Fellow – Immune Tolerance (Stanford University)

Postdoctoral Researcher – Autoimmunity and Antibody Engineering (Karolinska Institutet)

Project Leader – Immunology (Cellectis Inc.)

Postdoctoral Fellow – Immunology (Boston Children’s Hospital)

Postdoctoral Fellow – Genomic and Immunogenomic Aspects of Lymphomas (University of Chicago)

Principal Scientist – Antibody Discovery, Biologics Research (Janssen Research & Development LLC.)

Postdoctoral Fellow – Immunopathogenesis of Multiple Sclerosis (University of Iowa)

Senior Scientist – Immunology (National Institute of Immunology)

Assistant Professor – Immunology (Northwestern University)

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