Volume 5.24 | Jun 28

Immune Regulation News 5.24 June 28, 2013
Pulmonary Cell News
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Researchers Discover New Player Critical to Unleashing T Cells against Disease
Researchers provided new revelations about the intricate pathways involved in turning on T cells, the body’s most important disease-fighting cells. The team was the first to prove that a certain type of protein, called septins, play a critical role in activating a calcium channel on the surface of the T cell. The channel is the portal through which calcium enters T cells from the blood stream, an action essential for the T cell’s survival, activation, and ability to fight disease. [Press release from the La Jolla Institute for Allergy and Immunology discussing online prepublication in Nature] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
The Lymphoid Lineage-Specific Actin-Uncapping Protein Rltpr Is Essential for Costimulation via CD28 and the Development of Regulatory T Cells
The authors found that Rltpr was a lymphoid cell-specific, actin-uncapping protein essential for costimulation via CD28 and the development of regulatory T cells. [Nat Immunol] Abstract

Global Chromatin State Analysis Reveals Lineage-Specific Enhancers during the Initiation of Human T Helper 1 and T Helper 2 Cell Polarization
Naive CD4+ T cells can differentiate into specific helper and regulatory T cell lineages in order to combat infection and disease. The correct response to cytokines and a controlled balance of these populations is critical for the immune system and the avoidance of autoimmune disorders. To investigate how early cell-fate commitment is regulated, scientists generated the first human genome-wide maps of histone modifications that reveal enhancer elements after 72 hours of in vitro polarization toward T helper 1 and T helper 2 cell lineages. [Immunity] Abstract | Graphical Abstract

Tob1 Plays a Critical Role in the Activation of Encephalitogenic T Cells in CNS Autoimmunity
Investigators report that experimental autoimmune encephalomyelitis (EAE) in Tob1-/- mice was associated with augmented central nervous system (CNS) inflammation, increased infiltrating CD4+ and CD8+ T cell counts, and increased myelin-reactive Th1 and Th17 cells, with reduced numbers of regulatory T cells. [J Exp Med] Abstract | Press Release

Shp1 Regulates T Cell Homeostasis by Limiting IL-4 Signals
To define the T cell-intrinsic role of Shp1, researchers characterized mice with a T cell-specific Shp1 deletion (Shp1fl/fl CD4-cre). Surprisingly, thymocyte selection and peripheral TCR sensitivity were unaltered in the absence of Shp1. Instead, Shp1fl/fl CD4-cre mice had increased frequencies of memory phenotype T cells that expressed elevated levels of CD44. Activation of Shp1-deficient CD4+ T cells also resulted in skewing to the Th2 lineage and increased IL-4 production. [J Exp Med] Abstract

Melanoma Immunotherapy Using Mature DCs Expressing the Constitutive Proteasome
Since proteasomes generate peptides presented by HLA class I molecules, the authors hypothesized that mature melanoma antigen-loaded DCs engineered to process antigens through constitutive proteasomes would be superior inducers of antimelanoma immunity in vivo. [J Clin Invest] Full Article

Dysfunctional CD39POS Regulatory T Cells and Aberrant Control of T Helper Type 17 Cells in Autoimmune Hepatitis
Investigators described multiple CD39pos regulatory T cell defects that potentially contribute to the impaired immuno-regulation that is characteristic of autoimmune hepatitis. [Hepatology] Abstract

Plasmid-Encoded Proinsulin Preserves C-Peptide while Specifically Reducing Proinsulin-Specific CD8+ T Cells in Type 1 Diabetes
Scientists hypothesized that an engineered DNA plasmid encoding proinsulin (BHT-3021) would preserve β cell function in type 1 diabetes patients through reduction of insulin-specific CD8+ T cells. Proinsulin-reactive CD8+ T cells, but not T cells against unrelated islet or foreign molecules, declined in the BHT-3021 arm. No significant changes were noted in interferon-γ, interleukin-4 (IL-4), or IL-10 production in CD4 T cells. [Sci Transl Med] Abstract | Press Release

IL-22-Producing Neutrophils Contribute to Antimicrobial Defense and Restitution of Colonic Epithelial Integrity during Colitis
Using a dextran sodium sulfate-induced mouse model of acute colitis, the authors observed an interleukin (IL)-23-dependent up-regulation of IL-22 in the middle and distal colon at the onset of epithelial cell damage. This heightened IL-22 correlated with an influx of innate immune cells, suggesting an important role in colonic epithelial protection. Freshly isolated colon-infiltrating neutrophils produced IL-22 contingent upon IL-23 signaling, and IL-22 production was augmented by TNF-α. [Proc Natl Acad Sci USA] Abstract

CC-Chemokine Receptor 8 Potentiates Donor Treg Survival and Is Critical for the Prevention of Murine Graft-versus-Host Disease
Previous work suggested that early Treg migration into lymphoid tissue was important for graft-versus-host disease (GvHD) prevention. However, it is unclear how and where Tregs function longitudinally to affect GvHD. To better understand their mechanism of action, researchers studied two Treg-associated chemokine receptors in murine stem cell transplant models. [Blood] Abstract

Downregulation of Stat3 in Melanoma: Reprogramming the Immune Microenvironment as an Anticancer Therapeutic Strategy
Researchers investigated whether lentiviral (LV) delivery of Stat3-targeting short hairpin RNA (shRNA; LV-shStat3) to K1735-C4 melanoma cells modulates antitumor immunity. A single injection of LV-shStat3 in K1735-C4 tumors efficiently downregulated Stat3 in vivo and resulted in reduction of both vascular endothelial growth factor secretion and in myeloid-derived suppressor cell (MDSC) numbers. In contrast, the authors observed an increase in interleukin-6 and interferon-γ secretion, mature dendritic cells (DCs) and CD8+ T cells. Both DCs and CD8+ T cells displayed enhanced activity, whereas granulocytic MDSCs lost their suppressive capacity upon Stat3 downregulation. [Gene Ther] Abstract

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Putting the Brakes on Anticancer Therapies: Suppression of Innate Immune Pathways by Tumor-Associated Myeloid Cells
Tumor-associated myeloid cells are unique in that they are capable of manipulating responses to anticancer drugs by utilizing negative regulatory factors of innate immune pathways, including damage-associated molecule-mediated pattern recognition and tolerogenic phagocytosis. Further elucidation of the molecular mechanisms regulating innate immune responses of tumor-associated myeloid cells under cellular stress should enhance the development of new molecular targeting therapies for patients with treatment-refractory cancers. [Trends Mol Med] Abstract

Myeloid-Derived Suppressor Cells in Cancer: Recent Progress and Prospects
Immunosuppressive cells, mainly myeloid-derived suppressor cells (MDSCs) and T regulatory cells, downregulate antitumour immunity and cancer immunotherapy. In this article, the authors review data concerning the phenotypical and functional role of MDSCs in cancers. [Immunol Cell Biol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation field.  
EMD Serono Establishes Immuno-Oncology Research and Early Development Platform to Advance Innovation in Cancer Therapies
EMD Serono, Inc. announced its commitment to the field of cancer immunotherapy by creating a fully dedicated immuno-oncology innovation platform integrating research, early development and biomarker strategies. In addition to the company’s existing oncology platform, this new immuno-oncology platform will focus on developing therapies that leverage the immune system’s natural ability to fight tumors, and work in combination with existing and future therapies. [EMD Serono, Inc.] Press Release

Prima BioMed to Move Forward with Phase II Clinical Program for CVac in Pancreatic, Colorectal, and Triple-Negative Breast Cancers
Prima BioMed Ltd announced that it will move forward with three separate phase II clinical trials to evaluate the potential of CVac™ for the treatment of resectable pancreatic cancer, metastatic colorectal cancer, and triple-negative breast cancer. CVac is Prima’s lead product, a personalized immunocellular therapy targeted at mucin 1 overexpressing cancer cells, and in late phase trials for the treatment of epithelial ovarian cancer in remission. [Prima BioMed Ltd] Press Release

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NEW 2013 American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting
November 7-11, 2013
Baltimore, United States

Visit our events page to see a complete list of events in the immune regulation community.
NEW PhD Research Position – Molecular and Cellular Mechanisms of Immune Tolerance and Autoimmunity (Weizmann Institute of Science)

NEW Postdoctoral Position – Complement System in Acute and Chronic Inflammatory Diseases (Institute for Systemic Inflammation Research, University of Lübeck)

Postdoctoral Scientists – Immune Cell Biology (Medical Research Council – National Institute for Medical Research)

Postdoctoral Fellowship – Immune Regulation by Extracellular Matrix Proteins (Johns Hopkins University – School of Medicine)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

Junior or Senior Group Leader – Immunology/Infection/Inflammation (Center of Pathophysiology of Toulouse Purpan)

Postdoctoral Position – Mechanistic Studies in Immune Responses (Medical University of Vienna)

Postdoctoral Researcher – Innate Immunity (Massachusetts General Hospital / Harvard Medical School)

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